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in this issue CLINICAL

5 7 8 11

Cleveland Clinic’s drug information FAQ database: a rich resource. ED pharmacists document $225,000 in annual savings. In heart failure, baseline albumin may signal poor renal function. Protocols aim at reducing risk from fibrate–statin combinations.

OPERATIONS & MGMT

12 15

Compliance experts say time is now to plan for audits and surveys. Are you measuring up to CMS’ core measures? Here’s how to tell.

POLICY

New rules for reimbursement change the payment landscape.

EDUCATIONAL REVIEW

Immune Globulins: Therapeutic, Phamaceutical, Cost, and Administration Considerations See insert after page 4.

Volume 40 • Number 1 • January 2013

40th ANNIVERSARY YEAR 1972–2012

In Fight for Safe Compounding, a Salvo From NABP P

Smart Strategies for Savings Presented at ASHP Meeting Las Vegas—As the financial pressures on heaalth systems continue to mount, facilities are responding with a wide range of cost-cutting strategies, many of which were presented during the American Society of Health-System Pharmacists 2012 Midyear Clinical Meeeting. Whether it was billing for drug waste, putting limits on the use of o high-cost pancreatic enzymes or having pharmacy leaders manage employee e drug benefits—the latter racking up nearly $2 million in an nnual savings—all of the efforts shared a laudable goal: to conserve precious health care dollars without com mpromising patient care.

nspectors from the National Asso ociation of Boards of Pharmacy (NABP) and state pharmacy boards descended on six compoundingg pharmacies in four states during th he first two weeks of December as parrt of a broad, unified effort to bolsteer the safety of customized medicinees being shipped across state lines. The inspections were carried ou ut in California, New Jersey, Texas and Utah as public and political pressurre for increased federal and state regulaation of pharmacy compounders con ntinued to mount in the wake of th he fungal meningitis outbreak that, b by mid-December, had sickened morre than 650 individuals in 19 states and claimed nearly 40 lives. The dual inspection campaign is seet to continue well into 2013. It is parrt of the association’s contractual agreeement with the Iowa State Board o of Pharmacy to strengthen surveillancce of compounding pharmacies licensed

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The Overlook Medical Center in Summit, N.J., recouped more than $500,000 in 2011— m and d another $350,000 from January to August 2012—by ensuring that Medicare rreimbursed the hospital for discarded portions of biological aagents and other costly drugs. The payments were made possible by collaboration between the pharmacy and the hospital’ss Finance Department, which identified Centers for Medicarre & Medicaid Services (CMS) regulations allowing certain n levels of reimbursement for wasted medications from m single-use vials. (Multidose vials are not eligible for waste w reimbursement.)

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see NECC CRISIS, page 19 1

Heart Failure Programs Take Aim at Readmits Hollywood, Fla. and Las Vegas V — As part of the requirements of the Affordable Care Act, the Centers for Medicare & Medicaid Services (CMS) started imposing potential reimbursement penalties on hospitals based on their 30-day heart failure (HF) readmission rates beginning in October 2012. Concerned about these potential penalties, hospitals have ramped up efforts to forestall readmissions

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F Flushing Out the Waste IIn Unused Medications

see HF READMISSIONS, page 8

see SAVINGS, page 17

ADE Tracking ki May G Get Boost From New Reporting Software

n most health systems—even those with well-established electronic medical records—reporting adverse events is a spotty and not always standardized process. New software called KBCore may change that. In November, the program’s developer, CRG Medical, won the Reporting Patient Safety Events Challenge issued by the Office of the National Coordinator for Health Information Technology (ONC), in part due to the software’s flexibility: It enables users to generate error reports from any mobile

device or within the EMR simply by scanning a patient’s bar code. The program also is garnering positive reviews for the depth of relevant data that users can rapidly access. “Most reporting systems I’m familiar with don’t take advantage of the existing electronic data [they contain],” said Matt Grissinger, RPh, the director of error reporting programs at the Institute for Safe Medication Practices. “We already have the patient’s name, room number, the medications they’re on, their dosages and so

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see ADE TRACKING, page 3

The Book Page Clinical Skills for Pharmacists: A Patient-Focused Approach/Edition 3 Karen J. Tietze Visit mcmahonmedicalbooks.com

Sometimes appearances are everything. New FDA-approved IV premix drug labeling from Baxter. To help reduce medication errors due to incorrect drug selection, we redesigned the labeling for some of our most widely used liquid premix medications. We decreased the clutter and placed information in a consistent manner. Contact your Baxter sales representative to see how with change comes clarity.

Drug delivery from Baxter Healthcare Corporation. Doing our part, so you can do yours.

pharmacy workďŹ‚ow I drug delivery I nutrition I iv access I infusion systems I support & service

Baxter is a registered trademark of Baxter International Inc.

Medication Delivery

111779 12/12

Technology 3

Pharmacy Practice News • January 2013

Medication Safety

ADE TRACKING continued from page 1

on—yet [unlike KBCore], many systems make you re-enter [that information].” Although several other programs allow pharmacists to document their phone calls and let users pull patient data right into the program, “they’re not adverse event reporting programs like this one is,” Mr. Grissinger said. Jerry Fahrni, PharmD, a product manager at Talyst who frequently blogs on new pharmacy technologies and tweeted the news about KBCore, also sees the potential of the new software. “It’s a big deal to have all that information at your fingertips,” he said. “Every drug’s NDC [National Drug Code] number potentially can be found in the bar code, and by scanning it, this system can accurately populate the [fields for the] strength of the drug, the manufacturer and all the other data.” The program also allows for the input of additional information once the initial report has been submitted. KBCore was one of 13 submissions to the ONC Challenge, which evaluated reporting systems based on five factors: effectiveness; usability and design; innovation and creativity; integration with electronic medical records (EMRs) and secure transmission capabilities; and ability to leverage the nationwide health information network, an initiative for the exchange of health care information being developed under the auspices of ONC. “The platform itself was easy to use and clear to understand; we saw sub-

‘You could buy the Cadillac of [adverse event] reporting programs, but if your environment is punitive, it still won’t happen.’ —Matt Grissinger, RPh missions in this and other challenges that involve reporting, and input can be quite messy,” Adam Wong, a management and program analyst at the ONC, told InformationWeek Healthcare. “If the solution isn’t much easier to use than what already exists, it’s not moving things forward.”

No Gold Standard Yet Dr. Fahrni agreed that current adverse drug event reporting systems are in need of improvement. Indeed, at present, “there’s no nationally recognized gold standard system for adverse event reporting; there’s no software that really stands out,” he said. “In most hospitals today, people will do it manually. There’s no great way to collect that data and get it to a centralized spot.” Vicki Tamis, PharmD, BCPS, a clinical quality informaticist at PeaceHealth

Southwest Medical Center, in Vancouver, Wash., also sees flaws in how most hospitals manage the tracking and reporting of adverse drug events. “We find that people who submit reports into the electronic system don’t always get all the accurate information entered,” Dr. Tamis said. “Depending on the reporting program, sometimes the dosage information or route of administration isn’t correct.” Thus, the medication error report “is usually just a starting point. Almost every time you have to review a patient’s record for an adverse event or medication safety problem, it can take a lot of detective work to pull the full story together.” As for the KBCore software, Dr. Tamis said it looked promising. But she noted that it could be improved by adding an automated system response when specific drugs or doses of certain drugs

are given. “It would be nice if somebody could design a product that would automatically, if a certain dose of X medication is given, pull in [elements] of analysis you would need,” she said. While praising the KBCore application, Mr. Grissinger cautioned that any adverse event reporting program is only as good as the reporting culture at each hospital. “You could buy the Cadillac of reporting programs, but if your environment is punitive, it still won’t happen.” The other complaint ISMP hears frequently, he noted, “is that institutions have a big rollout of a reporting system and then people hear nothing and see no action being taken when they do report events. A program like this can make the process easier, but at the end of the day you have to change the culture.” —Gina Shaw

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Clinical 5

Pharmacy Practice News • January 2013

Practice Pearl

Development of a Drug Information FAQ Database Katie Stabi, PharmD Drug Information Pharmacist (REMS) Department of Pharmacy Cleveland Clinic Cleveland, Ohio

he Drug Information (DI) Center at the Cleveland Clinic serves as a resource for health care providers at 10 hospitals, more than 150 ambulatory clinics, and 15 ambulatory pharmacies in the Cleveland Clinic Health System. An internal electronic database, only accessible to the 8 DI pharmacists, stores more than 10 years of questions presented to the DI Center and answers the DI pharmacists provided. Often, staff pharmacists call specifically for the DI pharma-

cists to access the database if they know a question previously was answered. To share information stored in the internal database, a DI Frequently Asked Questions (FAQs) Database was created to be accessible by pharmacy staff. The database is intended to provide concise information about FAQs as well as hospital-specific clinical practice, information required in emergent situations, and information not readily available. The database is designed to be searchable by category (eg, Cleveland Clinic policy and procedures, crush/ administration, vaccines, immunoglobulins) or keyword. At first, only the DI staff submitted questions to be added to the database. However, as the database has gained more popularity and has

Can dabigatran capsules be opened for oral or feedingtube administration?

abigatran (Pradaxa, Boehringer Ingelheim) capsules should be swallowed whole and should NOT be broken, chewed, or opened before administration. The bioavailability of dabigatran etexilate increases by 75% when the pellets are taken without the capsule shell.

Source urce Prada axa (dabigatran etexilate mesylate) capsu ules for oral use [package insert]. Ridge efield, CT: Boehringer Ingelheim Pharm maceuticals, Inc; November 2011. Log Number: N 20669; Answ wered: 12/19/2011; Upda ated: 2/15/2012

been more widely used, staff pharmacists have contacted the DI Center with FAQs and responses to be added. Each response is written in a concise format and is referenced with the most current information and/or reflects standard clinical practice at the Cleveland Clinic. Responses are added to the DI FAQ Database after a peer-review process in which 2 DI pharmacists verify the validity and accuracy of the information. To ensure the DI FAQ database is used as a reference and not in place of a clinical decision-making process, there is a disclaimer that states: “This Frequently Asked Questions (FAQ) Database is intended for use as a REFERENCE ONLY. It is specific to adult patients (ie, >18 years) unless specified in the

response. Patient-specific factors (eg, age, weight, renal or hepatic function, comorbid conditions, concomitant medications) should ALWAYS be taken into account, along with the most current drug information, medical literature, and standards of practice.” In addition to having all sources listed in each response, the date when the response was added and the last-updated date are included. This information was included to assist the pharmacist in making a judgment call on whether there may be more up-to-date information available or if the DI Center should be contacted. All of the responses are given internal numbers for indexing and are in an annual rotation to be reviewed and updated with new information.

Can duloxetine capsules be opened for oral or feeding-tube administration?

uloxetine (Cymbalta, Lilly) delayed-release capsules contain enteric-coated pellets that should be swallowed whole and should NOT be chewed, crushed, or opened. The contents should NOT be sprinkled on food or mixed with liquid because doing so may affect the enteric coating. Duloxetine is listed on the “Do Not Crush” list by the Institute for Safe Medication Practices, Lexicomp, and Micromedex. The pellets should NOT be administered via feeding tube because that has not been studied and could potentially clog the feeding tube. Caution: There is an in vitro study that determined a 20-mg duloxetine capsule maintained its potency, purity, and dissolution when mixed with applesauce and apple juice (pH ~3.5). The efficacy and safety for oral administration was NOT tested. However, if this method is to be used, it is important that the pellets maintain their integrity and are NOT crushed, chewed, or broken. This study also found that the duloxetine pellets did NOT maintain potency, purity, and dissolution when mixed with chocolate pudding (pH ~5.5-6.0).

Sources Cymbalta (duloxetine) delayed-release capsules for oral use [package insert]. Indianapolis, IN: Lilly USA, LLC; September 2011. Mitchell JF. Orral dosage forms that should not be crushed. Institute for Safe Medication Practices. Oct 2011. http://www.ismp.org/tools/donotcrush.pdf. Accessed December D 19, 2011. Lexicom mp Online, Lexi-Drugs Online. Hudson, Ohio: Lexicomp, Inc; December 2011. (Search “crush.”) Microme edex Healthcare Series [Internet database]. Greenwood Village, CO: Thomson Reuters (Healthcare) Inc. Updated periodically. (Search ““crushed.”) Wells KA A, Losin WG. In vitro stability, potency, and dissolution of duloxetine enteric-coated pellets after exposure to applesauce, apple juice, and chocolate e pudding. Clin Ther. 2008;30:1300-1308. Log g Number: 20670; Answered: 12/19/2011; Updated: 2/15/2012

W Why is ideal body weight used to dose Gammagard Liquid 10% ((IV immunoglobulin)?

ammagard Liquid 10% (IV immunoglobulin [IVIG]; Baxter) is dosed by ideal body weight (IBW) due to standard Cleveland Clinic Foundation clinical practice. Adjusted body weight should be used if the total body weight is more than 30% to 40% of the IBW. IVIG has a low volume of distribution (0.09-0.13 L/kg) and is believed to stay primarily in the intravascular space with little distribution into the fat. There is limited published information available on dosing IVIG by IBW because the original studies used total body weight. However, several sources recommend using adjusted body weight in the obese population and suggest dosing with IBW may be an option for IVIG therapy.

Sources Standard Cleveland Clinic Foundation Clinical Practice. Immune Globulin Monograph. Lexicomp Online, Lexi-Drugs Online. Hudson, Ohio: Lexicomp, Inc; January 2012. Siegel J. Immunoglobulins and obesity. Pharmacy Practice News. 2010;37:8-9. Herman. Safe administration of intravenous immune globulin (IVIG). World of Drug Information. 2004;15. Khan S, Grimbacker B, Boecking C, et al. Serum trough IgG level and annual intravenous immunoglobulin dose are not related to body size in patients on regular replacement therapy. Drug Metab Lett. 2011;5:132-136. Rand K, Gibbs K, Derendorf H, Graham-Pole J. Pharmacokinetics of intravenous immunoglobulin (Gammagard) in bone marrow transplant patients. J Clin Pharmacol. 1991;31:1151-1154. Log Number: 20968; Answered: 1/24/2012; Updated: 2/24/2012

continued on page 6

6 Clinical

Pharmacy Practice News • January 2013

Practice Pearl continued from page 5

Does Zostavax (zoster vaccine live) need to be readministered if it was given intramuscularly instead of subcutaneously?

he Zostavax (zoster vaccine live) vaccine should be given subcutaneously in the deltoid region of the upper arm and not injected intravascularly or intramuscularly. However, if Zostavax is given intramuscularly, it does NOT need to be readministered.

Sources Department of Health and Human Services Centers for Disease Control and Prevention. Herpes zoster vaccination for health care professionals. http://www.cdc.gov/vaccines/vpd-vac/shingles/hcp-vaccination. htm. Accessed August 14, 2012. Zostavax (Zoster Vaccine Live) suspension for subcutaneous injection [package insert]. Whitehouse Station, NJ: Merck & Co., Inc.; June 2011. Log Number: 22571; Answered: 8/16/2012; Updated: 8/16/2012

Can the zoster vaccine live be given concurrently with the pneumonia vaccine?

he zoster vaccine live (Zostavax, Merck) and the pneumonia vaccine (Pneumovax 23, Merck) can be given to a patient on the same day. Although the manufacturer suggests that prescribers should consider administering Zostavax and Pneumovax 4 weeks apart, the Advisory Committee on Immunization Practices (ACIP) and the FDA support the administration of the 2 vaccines concomitantly. The vaccines should be administered using separate syringes at different anatomic sites.

Sources Zostavax (Zoster Vaccine Live) suspension for subcutaneous injection [package insert]. Whitehouse Station, NJ: Merck & Co, Inc; June 2011. Centers for Disease Control and Prevention. Prevention of herpes zoster: recommendations of the Advisory Committee on Immunization Practices (ACIP)–early release. MMWR Recomm Rep. 2008;57:e1-e31. Baylor NW. Letter to the editor: Perspective of the U.S. Food and Drug Administration on concomitant administration of Zostavax and Pneumovax. Vaccine. 2011;29:8771.

What medications containing caffeine can be used to treat postdural puncture headaches?

postdural puncture headache (PDPH) is a complication of spinal anesthesia or unintentional dural puncture. A PDPH usually is treated with IV caffeine/ sodium benzoate (500 mg in 1,000 mL normal saline administered over 1 hour, followed by 1,000 mL normal saline infused over 1 hour); a second course of caffeine can be given for unrelieved headache pain in 4 hours. The 500-mg dose of caffeine and sodium benzoate contains 250 mg of anhydrous caffeine and 250 mg of sodium benzoate, which helps increase the solubility of the caffeine. When caffeine/sodium benzoate is not available, 300 mg of oral anhydrous caffeine as a single dose can be used. Caffeine citrate oral solution is available as 20 mg/mL and contains 10 mg/mL of caffeine base. Therefore, 30 mL of caffeine citrate 20 mg/mL oral solution contains 300 mg of anhydrous caffeine.

Sources Lexicomp Online, Lexi-Drugs Online. Hudson, Ohio: Lexicomp, Inc; February 2012; February 15, 2012. Drug Evaluation: Caffeine. In: Hutchison TA, Shahan DR, Anderson ML, eds. Drugdex System [internet database]. Greenwood Village, CO: Thomson Healthcare; 2012. Updated periodically. Caffeine and sodium benzoate–caffeine injection, solution [package insert]. Shirley, NY: American Regent, Inc.; September 2008. Caffeine Citrate–caffeine citrate injection, solution [package insert]. Shirley, NY: American Regent, Inc.; September 2011. Camann WR, Murray RS, Mushlin PS, Lambert DH. Effects of oral caffeine on postdural puncture headache. A double-blind, placebo-controlled trial. Anesth Analg. 1990:70:181-184. Choi A, Laurito CE, Cunningham FE. Pharmacologic management of postdural puncture headache. Ann Pharmacother. 1996;30:831-839. Log Number: 21229; Answered: 2/27/2012; Updated: 4/20/2012

Are Imovax (human diploid cell rabies vaccine) and RabAvert (purified chick embryo cell rabies vaccine) interchangeable?

movax (human diploid cell rabies vaccine, Sanofi Pasteur) and RabAvert (purified chick embryo cell rabies vaccine, Novartis) are generically equivalent and are considered interchangeable. If available, the same brand should be used for the entire vaccination series. However, vaccination should NOT be deferred due to unavailability of the brand used for previous doses. A 2-year comparative study showed that the immunogenicity and reactogenicity of the 2 products are comparable. The dose, route, and indications of the 2 products are the same, but their origins, excipients, and side-effect profiles are different.

Sources

National Center for Immunization and Respiratory Diseases. General Recommendations on Immunization: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2011;60:8-9, 38. Log Number: 21004; Answered: 1/26/2012; Updated: 4/17/2012

How can copper be replenished in a copperdeficient patient?

he most appropriate dose, duration, route, and form of copper supplementation in copper-deficient patients (acquired copper deficiency, copper deficiency myelopathy) have not been studied. It is recommended to first discontinue any zinc therapy and use oral copper therapy, if needed, rather than IV therapy. However, IV therapy may be needed if the oral absorption of copper is blocked or if there is an urgent need due to the patient’s clinical condition. The preferred route is oral; 2 mg per day of elemental copper is usually sufficient, although doses as high as 9 mg per day have been used. Some sources recommend starting with 6 to 8 mg per day of elemental copper for 1 week, then decreasing the dose by 2 mg each week. Additionally, some sources recommend periodic reassessment of the serum copper level to determine if replacement therapy is adequate, and dose adjustment as needed. Oral therapy recommendations: Over-the-counter multivitamins are an option for oral therapy. The pharmacy usually stocks Therapeutic M (multivitamins, therapeutic with minerals PLUS IRON tablet [THEREMS-M]) tablets, which contain 2 mg of copper. It is important to read product labels to determine the amount of copper in the product. For example, Centrum Kids complete chewable tablets contain 2 mg copper per tablet, whereas Centrum Silver tablets contain 0.5 mg copper per tablet. There are no FDA-approved singleingredient products available, and, per hospital policy, dietary supplements that are not FDA-approved will not be ordered, stocked, or dispensed. IV therapy recommendations: 2 mg per day of elemental copper infused over 2 hours for 5 days, then periodically thereafter. IV copper is available as single-entity cupric sulfate (0.4 mg elemental copper/mL) and cupric chloride (0.4 mg elemental copper/mL), with the primary indication for use as an additive in parenteral nutrition. Verify with the IV room that an IV product is available because both products recently have been in short supply.

Sources Kumar N. Copper deficiency myelopathy (Human Swayback). Mayo Clin Proc. 2006;81(10):1371-1384. Jaiser SR, Winston GP. Copper deficiency myelopathy. J Neurol. 2010;257:869-881. Product Information. Therems-M vitamin and mineral supplement. Rugby Laboratories, Inc. http://www.watson.com/products/product-database-detail.asp?currentPage=2&group=alpha&c=T. Accessed May 31, 2012. Centrum.com. Accessed December 20, 2011. Cleveland Clinic Pharmacy. Policy Number 03-055. Dietary Supplements: Formulary. Effective Date 02/08/07, Dates Revised 02/23/10, 04/02/12. Log Number: 22114; Answered: 6/21/2012; Updated: 6/21/2012

Grabenstein JD. ImmunoFacts: Vaccines and Immunologic Drugs–2012 (37th revision). St. Louis, MO: Wolters Kluwer Health; 2011. Dreesen DW, Fishbein DB, Kemp DT, Brown J. Two-year comparative trial on the immunogenicity and adverse effects of purified chick embryo cell rabies vaccine for pre-exposure immunization. Vaccine. 1989;7:397-400. Manning SE, Rupprecht CE, Fishbein D, et al. Human rabies prevention–United States, 2008: recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2008;57:1-28. Imovax Rabies (rabies vaccine, HDCV) [package insert]. Swiftwater, PA: Sanofi Pasteur, Inc.; December 2005. RabAvert (rabies vaccine) [package insert]. Emeryville, CA: Novartis Vaccines and Diagnostics, Inc.; March 2010. Log Number: 21038; Answered: 1/31/2012; Updated: 3/29/2012

The FAQ DI Database is used frequently by the DI staff and was accessed by y pharmacy staff more than 2,000 times over a recent 6-month period. The FAQ DI Database would not be possible without the help of Mandy Leonard, PharmD, Janine Douglas, PharmD, Matthew Miller, CIS, and the drug information pharmacist peerr reviewers: Marigel Constantiner, RPh, Meghan Lehmann, PharmD, Mandy Leonard, PharmD, Amy Martin, PharmD, Kara Sink, RPh, Christopher Snyder, RPh, and Marcia Wyman, PharmD.

Clinical 7

Pharmacy Practice News • January 2013

Critical Care

Starting an Emergency Department Pharmacy at Low Cost

‘This study is a good demonstration of how even in these [challenging economic] times, new programs like this can be initiated to help improve patient care at the hospital.’ —Bhavik Nana, PharmD Dr. Nana said he is proud of the successes documented in the study. “This is a challenging time for the health care

field,” he stressed. “One of the challenges health care facilities are facing is [reduced] reimbursement rates. We

have to work harder with the same limited resources. This study is a good

•

see PHARM COST, page 14

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n tough economic times, it is still possible to start an emergency department (ED) pharmacy and actually save money in the process. That is the experience reported in a study of an ED pharmacy at Franciscan Saint Margaret Health (FSMH), in Hammond, Ind (Am ( J Health Syst Pharm 2012;69:1682-1686). By shifting existing staff pharmacists to the ED to perform medication reconciliation, the hospital documented $225,000 in cost savings and also improved the accuracy of reconciliation efforts. From the start, the ED pharmacy initiative at FSMH was focused on medication reconciliation. But its use of existing pharmacy staff to perform that task was something of a pivot for the program, lead author Bhavik Nana, PharmD, told Pharmacy Practice News. The hospital initially had received approval to hire three pharmacy technicians for the program, but because of economic conditions, the planned positions were eliminated. If an ED pharmacy were to be established, it would need to begin with no additional funding for technicians or pharmacists. “That’s basically what we did,” Dr. Nana noted. To launch the program, two pharmacists were secured for the ED program from FSMH’s existing full-time equivalent (FTE) staff. Staffing schedules were adjusted, with the pharmacists providing ED services from 11:30 a.m. to 5:30 p.m. on weekdays. The manager of the central order-entry pharmacy agreed to expand hours of coverage at no additional cost. A small, centrally located area in the ED became an ED pharmacy workspace. The two pharmacists received training in admission medication reconciliation and critical care drugs, and were certified in advanced cardiac life support and pediatric advanced life support. Commercially available pharmacy intervention software was used to document interventions. A retrospective chart review of a random sample of admission medication reconciliations (N=102) showed that 90.2% of reconciliations (46 of 51) performed by pharmacists were accurate compared with 66.7% of those (34 of 51) performed by nurses ((P<0.05). A survey of ED admitting nurses and physicians found that the ED pharmacists were well received. Annualized cost savings attributable to pharmacist activities totaled $225,000, including both soft-dollar and harddollar cost savings. Soft-dollar cost savings resulted from projected cost avoidance, for example, owing to medication reconciliations; hard-dollar cost savings resulted directly from accepting a pharmacist recommendation, such as for a drug choice.

MediDose.com

8 Clinical

Pharmacy Practice News • January 2013

Cardiology

HF READMISSIONS

Atlanta. “All patients who are in the moderate to high–risk group will have a pharmacy consult and follow-up.”

continued from page 1

among those in this vulnerable target population, and several abstracts presented at recent pharmacy meetings suggest that pharmacist-led multidisciplinary efforts, including patient drug education and follow-up, can lower hospital readmission rates related to HF. “Many institutions are trying their best to come up with methods to meet the requirements, and pharmacists are an integral part of the solution,” said Robert Lee Page II, PharmD, an associate professor of clinical pharmacy and a physical medicine clinical specialist in the Division of Cardiology at the University of Colorado School of Pharmacy and Medicine, in Aurora. “Every hospital has its own different case mix, but these studies show we can all learn from each other.”

A Coordinated Multidisciplinary Approach Works Responding to the threat of possible financial penalties, researchers at The Nebraska Medical Center, in Omaha, conducted a study involving pharmacists, nurses and nutritionists to help lower readmission rates. The study included early identification of patients with HF upon admission, interdisciplinary education during the inpatient stay and interdisciplinary follow-up phone calls after discharge. “I was surprised that our efforts not only improved the patients’ understanding of the disease process but also enhanced their resolve and commitment to take their medications and pay more attention to their symptoms,” said Brian Trevarrow, PharmD, the lead researcher, who presented the study at the American College of Clinical Pharmacy (ACCP) annual meeting. The educational efforts—which focused on the pharmacologic effects on disease pathophysiology, possible side effects, dosing, regimen adherence, drug interactions and special instructions— were initiated in January 2011. Pharmacists, nurses and nutritionists all called patients four times: 24 to 48 hours after discharge, within one week, at three to four weeks and again after 30 days. The team retrospectively analyzed the readmissions of 532 patients in 2010 (pre-education group) and prospectively analyzed the readmissions of 482 patients exposed to the education program in 2011. The two groups of patients had comparable comorbidities and demographics and were taking similar medications. The rate of all-cause readmission was significantly reduced after implementation of the multidisciplinary program, from 28% in 2010 to 20% in 2011. The incidence of HF readmissions also decreased from 12% to 5%. The follow-up efforts were ambitious

Pharmacist-Managed Medication Optimization

and rewarding, said Dr. Trevarrow, the coordinator of the Anticoagulation Stewardship and Heart Failure program at the medical center, and a clinical assistant professor at the University of Nebraska College of Pharmacy, in Omaha. “Patients [had been] taking medications for years just because they were told to,” said Dr. Trevarrow, noting that after the program was initiated, several patients thanked him for explaining how the medications work and why it was important to take them.

Patient Education and Follow-Up A second study presented at the ACCP meeting also underscored the value of helping patients understand the importance of taking their medications and showed lower hospital readmission rates when pharmacists were involved in patient care during the hospital stay as well as after discharge. During the study, investigators evaluated patients admitted to Atlanta Medical Center with a primary or secondary

diagnosis of HF between Aug. 1, 2011 and Jan. 30, 2012, randomizing them into control (n=38) and intervention (n=22) groups. The baseline characteristics, which included ejection fraction, hospital length of stay and comorbidities, were similar between the populations. Control group patients received the standard of care. Intervention group patients received one-on-one medication and disease management discharge counseling from a pharmacist. Patients were called 14 and 28 days after discharge. The 30-day readmission rate for patients in the intervention group (9.5%) was approximately 50% lower than for the patients in the control group (21%). “Heart failure patients are at risk for coming back to the hospital soon after discharge. Because of this pilot study, we now have a program where patients are screened for readmission risk,” said Pamela M. Moye, PharmD, the lead researcher and a clinical assistant professor in the Department of Pharmacy Practice at Mercer University, in

Baseline Albumin Predicts Worsening Renal Function in Heart Failure Patients

OLLYWOOD,

FLA.—Albumin levels less than or equal to 3 g/dL signal worsening renal failure (WRF) in patients with acute decompensated heart failure (ADHF), according to a recent University of Michigan study presented at the ACCP annual meeting. “Our study looked at baseline characteristics to help predict which patients receiving continuous infusions of loop diuretics were predisposed to develop WRF, whereas other research has studied what happened during infusion, when it may be too late to prevent WRF,” said Megan Barnes, PharmD, the lead researcher and a clinical pharmacy specialist in cardiology at West Penn Allegheny Health System, in Pittsburgh. Aggressive diuresis with loop diuretic infusions often is necessary for symptom relief in patients hospitalized for ADHF, said Dr. Barnes. But it can lead to development of WRF, which has been associated with increased mortality. Dr. Barnes and her team performed a retrospective observational analysis of 177 patients with ADHF who were receiving continuous infusions of loop diuretics. The study included all patients who were admitted to the University of Michigan Health System with ADHF between January 2006 and June 2009 and received the infusions. WRF was defined as an increase of at least 0.3 mg/dL from the baseline serum creatinine value. The mean patient age was 61 years and the median length of loop diuretic infusion was four days. Forty-eight patients (27%) experienced WRF and 34 (19%) died during hospitalization. A myriad of other factors were considered as predictors of WRF, including advanced age, severity of HF, baseline demographics, comorbidities and medications. “It’s not surprising that low albumin would be a predictor, because it’s also indicative of nutritional status,” said Robert Page II, PharmD, MSPH, an associate professor of clinical pharmacy and a physical medicine clinical specialist in the Division of Cardiology at the University of Colorado School of Pharmacy and Medicine, in Aurora. “If patients are nutritionally depleted, it makes sense they may not fare well with high-dose diuretics.” —D.H.S. Drs. Barnes and Page reported no relevant ﬁnancial conﬂicts of interest.

A third related ACCP study dealt with the chronic problem of underdosing cardiac medications, such as angiotensin-converting enzyme inhibitors (ACEIs) and β-blockers in the treatment of HF. National guidelines recommend maximizing therapy to reduce mortality and the number of rehospitalizations. Pharmacists from the University of Illinois at Chicago (UIC) managed a clinic for a half-day every other week to help patients maximize their ACEIs and β-blockers. At each visit, the pharmacist reviewed vitals, symptoms, educational needs, laboratory results and medication regimens. ACEIs and β-blockers were titrated as tolerated. Since the clinic opened in July 2011, the HF pharmacist has made 126 visits to 46 patients, and 64% of cardiologists referred their patients to the clinic for medication optimization. The program was so successful that within a month, the half-day clinic had to operate every week. “What’s unique is that it lets me work independently. I don’t need to call a physician before I make a medication adjustment,” said Vicki L. Groo, PharmD, the lead researcher and a clinical pharmacist at UIC. Prescriptions and the progress note are sent to the referring cardiologist for cosignature. The clinic pharmacist sees patients at two-week intervals, with a cardiologist available for additional consultation as needed. Pharmacist services at the clinic are billed via a hospital-based facility fee model at a level 3 or 4 technical fee, depending on visit complexity. Dr. Groo said that because she was already working in the university’s Heart Center, the costs of implementing this new clinic were minimal. The fact that UIC is getting “some reimbursement for pharmacy services … shows that their services are valued,” said Dr. Page, adding, “In order to sustain a program, you need reimbursement.”

VA Hospital Looks for Clues A study presented at the American Society of Health-System Pharmacists (ASHP) Midyear Clinical Meeting evaluated the factors leading to HF readmissions at the Jesse Brown Veterans Affairs Medical Center, in Chicago. At the VA medical center, like at UIC, underdosing was a factor contributing to HF readmissions. The VA team retrospectively evaluated patients with a HF diagnosis who were discharged from the medical center between Oct. 1, 2010 and March 1, 2011, comparing those who were readmitted

•

see HF READMISSIONS, page 11

LEVETERACITAM INJECTION, USP

Rx Only

INDICATIONS AND USAGE-Levetiracetam injection is an antiepileptic drug indicated for adjunct therapy in adult patients (16 years and older) when oral administration is temporarily not feasible. Partial Onset Seizures-Levetiracetam is indicated as adjunctive therapy in the treatment of partial onset seizures in adults with epilepsy. Myoclonic Seizures in Patients with Juvenile Myoclonic Epilepsy-Levetiracetam is indicated as adjunctive therapy in the treatment of myoclonic seizures in adults with juvenile myoclonic epilepsy. Primary Generalized Tonic-Clonic Seizures-Levetiracetam is indicated as adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in adults with idiopathic generalized epilepsy. CONTRAINDICATIONS-None WARNINGS AND PRECAUTIONS Neuropsychiatric Adverse Reactions Partial Onset Seizures - In some adults experiencing partial onset seizures, levetiracetam causes the occurrence of central nervous system adverse reactions that can be classified into the following categories: 1) somnolence and fatigue, 2) coordination difficulties, and 3) behavioral abnormalities. In controlled trials of adult patients with epilepsy experiencing partial onset seizures, 14.8% of levetiracetam-treated patients reported somnolence, compared to 8.4% of placebo patients. There was no clear dose response up to 3000 mg/day. In a study where there was no titration, about 45% of patients receiving 4000 mg/day reported somnolence. The somnolence was considered serious in 0.3% of the treated patients, compared to 0% in the placebo group. About 3% of levetiracetam-treated patients discontinued treatment due to somnolence, compared to 0.7% of placebo patients. In 1.4% of treated patients and in 0.9% of placebo patients the dose was reduced, while 0.3% of the treated patients were hospitalized due to somnolence. In controlled trials of adult patients with epilepsy experiencing partial onset seizures, 14.7% of treated patients reported asthenia, compared to 9.1% of placebo patients. Treatment was discontinued in 0.8% of treated patients as compared to 0.5% of placebo patients. In 0.5% of treated patients and in 0.2% of placebo patients the dose was reduced. A total of 3.4% of levetiracetam-treated patients experienced coordination difficulties, (reported as either ataxia, abnormal gait, or incoordination) compared to 1.6% of placebo patients. A total of 0.4% of patients in controlled trials discontinued levetiracetam treatment due to ataxia, compared to 0% of placebo patients. In 0.7% of treated patients and in 0.2% of placebo patients the dose was reduced due to coordination difficulties, while one of the treated patients was hospitalized due to worsening of pre-existing ataxia. Somnolence, asthenia and coordination difficulties occurred most frequently within the first 4 weeks of treatment. In controlled trials of patients with epilepsy experiencing partial onset seizures, 5 (0.7%) of levetiracetam-treated patients experienced psychotic symptoms compared to 1 (0.2%) placebo patient. Two (0.3%) levetiracetam-treated patients were hospitalized and their treatment was discontinued. Both events, reported as psychosis, developed within the first week of treatment and resolved within 1 to 2 weeks following treatment discontinuation. Two other events, reported r as hallucinations, occurred after 1 to 5 months and resolved within 2 to 7 days while the patients remained on treatment. In one patient experiencing psychotic depression occurring within a month, symptoms resolved within 45 days while the patient continued treatment. A total of 13.3% of levetiracetam patients experienced other behavioral symptoms (reported as aggression, agitation, anger, anxiety, apathy, depersonalization, depression, emotional lability, hostility, irritability, etc.) compared to 6.2% of placebo patients. Approximately half of these patients reported these events within the first 4 weeks. A total of 1.7% of treated patients discontinued treatment due to these events, compared to 0.2% of placebo patients. The treatment dose was reduced in 0.8% of treated patients and in 0.5% of placebo patients. A total of 0.8% of treated patients had a serious behavioral event (compared to 0.2% of placebo patients) and were hospitalized. In addition, 4 (0.5%) of treated patients attempted suicide compared to 0% of placebo patients. One of these patients completed suicide. In the other 3 patients, the events did not lead to discontinuation or dose reduction. The events occurred after patients had been treated for between 4 weeks and 6 months.

Myoclonic Seizuress -During clinical development, the number of patients with myoclonic seizures exposed to levetiracetam was considerably smallerr than the number with partial seizures. Therefore, under-reporting of certain adverse reactions was more likely to occur in the myoclonic seizure population. In some patients experiencing myoclonic seizures, levetiracetam causes somnolence and behavioral abnormalities. It is expected that the events seen in partial seizure patients would occur in patients with JME. In the double-blind, controlled trial in patients with juvenile myoclonic epilepsy experiencing myoclonic seizures, 11.7% of levetiracetam-treated patients experienced somnolence compared to 1.7% of placebo patients. No patient discontinued treatment as a result of somnolence. In 1.7% of levetiracetam-treated patients and in 0% of placebo patients the dose was reduced as a result of somnolence. Non-psychotic behavioral disorders (reported as aggression and irritability) occurred in 5% of the levetiracetam-treated patients compared to 0% of placebo patients. Non-psychotic mood disorders (reported as depressed mood, depression, and mood swings) occurred in 6.7% of levetiracetam-treated patients compared to 3.3% of placebo patients. A total of 5.0% of levetiracetam-treated patients had a reduction in dose or discontinued treatment due to behavioral or psychiatric events (reported as anxiety, depressed mood, depression, irritability, and nervousness), compared to 1.7% of placebo patients. Primary Generalized Tonic-Clonic Seizures During clinical development, the number of patients with primary generalized tonic-clonic epilepsy exposed to levetiracetam was considerably smaller than the number with partial epilepsy, described above. As in the partial seizure patients, behavioral symptoms appeared to be associated with levetiracetam treatment. Gait disorders and somnolence were also described in the study in primary generalized seizures, but with no difference between placebo and levetiracetam treatment groups and no appreciable discontinuations. Although it may be expected that drug related events seen in partial seizure patients would be seen in primary generalized epilepsy patients (e.g., somnolence and gait disturbance), these events may not have been observed because of the smaller sample size.In some patients experiencing primary generalized tonic-clonic seizures, levetiracetam causes behavioral abnormalities. In the double-blind, controlled trial in patients with idiopathic generalized epilepsy experiencing primary generalized tonic-clonic seizures, irritability was the most frequently reported psychiatric adverse event occurring in 6.3% off levetiracetam-treated patients compared to 2.4% of placebo patients. Additionally, non-psychotic behavioral disorders (reported as abnormal behavior, aggression, conduct disorder, and irritability) occurred in 11.4% of the levetiracetam-treated patients compared to 3.6% of placebo patients. Of the levetiracetam-treated patients experiencing non-psychotic behavioral disorders, one patient discontinued treatment due to aggression. Non-psychotic mood disorders (reported as anger, apathy, depression, mood altered, mood swings, negativism, suicidal ideation, and tearfulness) occurred in 12.7% of levetiracetam-treated patients compared to 8.3% of placebo patients. No levetiracetam-treated patients discontinued or had a dose reduction as a result of these events. One levetiracetam-treated patient experienced suicidal ideation. One patient experienced delusional behavior that required the lowering of the dose of levetiracetam. In a long-term open label study that examined patients with various forms of primary generalized epilepsy, along with the non-psychotic behavioral disorders, 2 of 192 patients studied exhibited psychotic-like behavior. Behavior in one case was characterized by auditory hallucinations and suicidal thoughts and led to levetiracetam discontinuation. The other case was described as worsening of pre-existent schizophrenia and did not lead to drug discontinuation. Withdrawal Seizures-Antiepileptic drugs, including levetiracetam, should be withdrawn gradually to minimize the potential of increased seizure frequency. Hematologic Abnormalitiess -Partial Onset Seizures -Minor, but statistically significant, decreases compared to placebo in total mean RBC count (0.03 x 106/mm3), mean hemoglobin (0.09 g/dL), and mean hematocrit (0.38%), were seen in levetiracetam-treated patients in controlled trials. A total of 3.2% of treated and 1.8% of placebo patients had at least one possibly significant ()2.8 x 109/L) decreased WBC, and 2.4% of treated and 1.4% of placebo patients had at least one possibly significant ()1.0 x 109/L) decreased neutrophil count. Of the treated patients with a low neutrophil count, all but one rose towards or to baseline with continued treatment. No patient was discontinued secondary to low neutrophil counts. Juvenile Myoclonic Epilepsyy -Although there were no obvious hematologic abnormalities observed in patients with JME, the limited number of patients makes any conclusion tentative. The data from the partial seizure patients should be considered to be relevant for JME patients. Hepatic Abnormalities-There were no meaningful changes in mean liver function tests (LFT) in controlled trials in adult patients; lesser LFT abnormalities were similar in drug and placebo treated patients in controlled trials (1.4%). No patients were discontinued from controlled trials for LFT abnormalities except for 1 (0.07%) adult epilepsy patient receiving open treatment. ADVERSE REACTIONS Clinical Studies Experience-Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The adverse reactions that result from levetiracetam injection use include all of those reported for levetiracetam tablets and oral solution. Equivalent doses of intravenous (IV) levetiracetam and oral levetiracetam result in equivalent Cmax, Cmin, and total systemic exposure to levetiracetam when the IV levetiracetam is administered as a 15 minute infusion. The prescriber should be aware that the adverse reaction incidence figures in the following tables, obtained when levetiracetam was added to concurrent AED therapy, cannot be used to predict the frequency of adverse experiences in the course of usual medical practice where patient characteristics and other factors may differ from those prevailing during clinical studies. Similarly, the cited frequencies cannot be directly compared with figures obtained from other clinical investigations involving different treatments, uses, or investigators. An inspection of these frequencies, however, does provide the prescriber with one basis to estimate the relative contribution of drug and non-drug factors to the adverse reaction incidences in the population studied. Partial Onset Seizures Table 3 lists treatment-emergent adverse reactions that occurred in at least 1% of adult epilepsy patients treated with levetiracetam tablets participating in placebocontrolled studies and were numerically more common than in patients treated with placebo. In these studies, either levetiracetam or placebo was added to concurrent AED therapy. Adverse reactions were usually mild to moderate in intensity. Table 3: Incidence (%) of Treatment-Emergent Adverse Reactions in Placebo-Controlled, Add-On Studies in Adults Experiencing Partial Onset Seizures by Body System (Adverse Reactions Occurred in at Least 1% of Levetiracetam-Treated Patients and Occurred More Frequently than Placebo-Treated Patients) Body System/Adverse Reaction Levetiracetam Placebo (N=769)% (N=439)% Body as a Whole Asthenia Headache Infection Pain Digestive System

15 14 13 7

9 13 8 6

Anorexia Nervous System Somnolence Dizziness Depression Nervousness Ataxia Vertigo Amnesia Anxiety Hostility Paresthesia Emotional Lability Respiratory System

15 9 4 4 3 3 2 2 2 2 2

8 4 2 2 1 1 1 1 1 1 0

Pharyngitis Rhinitis Cough Increased Sinusitis Special Senses

6 4 2 2

4 3 1 1

Diplopia

Myoclonic Seizures Table 4 lists treatment-emergent adverse reactions that occurred in at least 5% of juvenile myoclonic epilepsy patients experiencing myoclonic seizures treated with levetiracetam tablets and were numerically more common than in patients treated with placebo. In this study, either levetiracetam or placebo was added to concurrent AED therapy. Adverse reactions were usually mild to moderate in intensity. Table 4: Incidence (%) of Treatment-Emergent Adverse Reactions in a Placebo-Controlled, Add-On Study in Patients with Myoclonic Seizures by Body System (Adverse Reactions Occurred in at Least 5% of Levetiracetam-Treated Patients and Occurred More Frequently than Placebo-Treated Patients) Body System/Adverse Reaction Levetiracetam Placebo (N=60)% (N=60)% Ear and labyrinth disorders Vertigo Infections and infestations

Pharyngitis Inﬂuenza

7 5

0 2

Neck pain Nervous system disorders

Somnolence Psychiatric disorders

Depression

Musculoskeletal and connective tissue disorders

Primary Generalized Tonic-Clonic Seizure Table 5 lists treatment-emergent adverse reactions that occurred in at least 5% of idiopathic generalized epilepsy patients experiencing PGTC seizures treated with levetiracetam and were numerically more common than in patients treated with placebo. In this study, either levetiracetam or placebo was added to concurrent AED therapy. Adverse reactions were usually mild to moderate in intensity. Table 5: Incidence (%) of Treatment-Emergent Adverse Reactions in a Placebo-Controlled, Add-On Study in Patients 4 Years of Age and Older with PGTC Seizures by MedDRA System Organ Class (Adverse Reactions Occurred in at Least 5% of Levetiracetam-Treated Patients and Occurred More Frequently than Placebo-Treated Patients) Body System/Adverse Reaction Levetiracetam Placebo (N=79)% (N=84)% Gastrointestinal disorders Diarrhea

Fatigue Infections and infestations

Nasopharyngitis Psychiatric disorders

Irritability Mood swings

6 5

2 1

General disorders and administration site conditions

DRUG INTERACTIONS In vitroo data on metabolic interactions indicate that levetiracetam is unlikely to produce, or be subject to, pharmacokinetic interactions. Levetiracetam and its major metabolite, at concentrations well above Cmax levels achieved within the therapeutic dose range, are neither inhibitors of nor high affinity substrates for human liver cytochrome P450 isoforms, epoxide hydrolase or UDP-glucuronidation enzymes. In addition, levetiracetam does not affect the in vitro glucuronidation of valproic acid. Levetiracetam circulates largely unbound (<10% bound) to plasma proteins; clinically significant interactions with other drugs through competition for protein binding sites are therefore unlikely. Potential pharmacokinetic interactions were assessed in clinical pharmacokinetic studies (phenytoin, valproate, oral contraceptive, digoxin, warfarin, probenecid) and through pharmacokinetic screening in the placebo-controlled clinical studies in epilepsy patients. USE IN SPECIFIC POPULATIONS Pregnancy-Pregnancy Category C-There are no adequate and well-controlled studies in pregnant women. In animal studies, levetiracetam produced evidence of developmental toxicity, including teratogenic effects, at doses similar to or greater than human therapeutic doses. Levetiracetam should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Administration to female rats throughout pregnancy and lactation led to increased incidences of minor fetal skeletal abnormalities and retarded offspring growth pre- and/or postnatally at doses *350 mg/kg/day (approximately equivalent to the maximum recommended human dose of 3000 mg [MRHD] on a mg/m2 basis) and with increased pup mortality and offspring behavioral alterations at a dose of 1800 mg/kg/day (6 times the MRHD on a mg/m2 basis). The developmental no effect dose was 70 mg/kg/day (0.2 times the MRHD on a mg/m2 basis). There was no overt maternal toxicity at the doses used in this study. Treatment of pregnant rabbits during the period of organogenesis resulted in increased embryo fetal mortality and increased incidences of minor fetal skeletal abnormalities at doses *600 mg/kg/day (approximately 4 times MRHD on a mg/m2 basis) and in decreased fetal weights and increased incidences of fetal malformations at a dose of 1800 mg/kg/day (12 times the MRHD on a mg/m2 basis). The developmental no effect dose was 200 mg/kg/day (1.3 times the MRHD on a mg/m2 basis). Maternal toxicity was also observed at 1800 mg/kg/day. When pregnant rats were treated during the period of organogenesis, fetal weights were decreased and the incidence of fetal skeletal variations was increased at a dose of 3600 mg/kg/day (12 times the MRHD). 1200 mg/kg/day (4 times the MRHD) was a developmental no effect dose. There was no evidence of maternal toxicity in this study. Treatment of rats during the last third of gestation and throughout lactation produced no adverse developmental or maternal effects at doses of up to 1800 mg/kg/day (6 times the MRHD on a mg/m2 basis). Patients may enroll in the North American Antiepileptic Drug Pregnancy Registry by calling (888) 233-2334 (toll free). Labor and Delivery-The effect of levetiracetam on labor and delivery in humans is unknown. Nursing Mothers-Levetiracetam is excreted in breast milk. Because of the potential for serious adverse reactions in nursing infants from levetiracetam, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. Pediatric Use-Safety and effectiveness of levetiracetam injection in patients below the age of 16 years have not been established. Geriatric Use-Of the total number of subjects in clinical studies of levetiracetam, 347 were 65 and over. No overall differences in safety were observed between these subjects and younger subjects. There were insufficient numbers of elderly subjects in controlled trials of epilepsy to adequately assess the effectiveness of levetiracetam in these patients. A study in 16 elderly subjects (age 61 to 88 years) with oral administration of single dose and multiple twice-daily doses for 10 days showed no pharmacokinetic differences related to age alone. Levetiracetam is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. Use in Patients with Impaired Renal Function-Clearance of levetiracetam is decreased in patients with renal impairment and is correlated with creatinine clearance. Caution should be taken in dosing patients with moderate and severe renal impairment and in patients undergoing hemodialysis. The dosage should be reduced in patients with impaired renal function receiving levetiracetam and supplemental doses should be given to patients after dialysis. OVERDOSAGE Signs, Symptoms and Laboratory Findings of Acute Overdosage in Humans The highest known dose of oral levetiracetam received in the clinical development program was 6000 mg/day. Other than drowsiness, there were no adverse reactions in the few known cases of overdose in clinical trials. Cases of somnolence, agitation, aggression, depressed level of consciousness, respiratory depression and coma were observed with levetiracetam overdoses in postmarketing use. Treatment or Management of Overdosee - There is no specific antidote for overdose with levetiracetam. If indicated, elimination of unabsorbed drug should be attempted by emesis or gastric lavage; usual precautions should be observed to maintain airway. General supportive care of the patient is indicated including monitoring of vital signs and observation of the patient’s clinical status. A Certified Poison Control Center should be contacted for up to date information on the management of overdose with levetiracetam. Hemodialysiss- Standard hemodialysis procedures result in significant clearance of levetiracetam (approximately 50% in 4 hours) and should be considered in cases of overdose. Although hemodialysis has not been performed in the few known cases of overdose, it may be indicated by the patient’s clinical state or in patients with significant renal impairment. Storage-Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) (See USP Controlled Room Temperature). How Supplied-Levetiracetam injection 500 mg/5 mL is a clear, colorless, sterile solution. It is supplied in single-use 5 mL vials, available in cartons of 25 vials (NDC 0517-3605-25).

AR126 Iss. Date 1/2012

Clinical 11

Pharmacy Practice News • January 2013

Cardiology

Fibrate–Statin Label Changes Call for New Protocols Las Vegas—In 2011, the FDA warned clinicians against using the fibrate gemfibrozil with simvastatin because of an increased risk for cardiomyopathy and rhabdomyolysis in patients taking the combination therapy. Some health systems have responded by issuing a universal ban on all fibrate–statin combination treatment. Others have incorporated a hard stop into their clinical decision support systems when these two drugs are co-prescribed. Regardless of the approach, experts say that safety protocols to monitor lipids and replace gemfibrozil with an appropriate alternative or switch to another statin must be part of the mix to guard against adverse drug reactions. Several efforts to accomplish those medication management goals were in evidence at the American Society of Health-System Pharmacists (ASHP) Midyear Clinical Meeting.

An Algorithm-Based Approach In response to the gemfibrozil–simvastatin contraindication, the Pharmacy and Therapeutics Committee at the Ralph H. Johnson Veterans Affairs Medical Center (RHJ VAMC), in Charleston, S.C., has developed a treatment algorithm based on patients’ low-density lipoprotein (LDL) cholesterol and triglyceride levels. The algorithm calls for patients whose LDL is “at goal” (<130 mg/dL for primary prevention patients and <100 mg/dL for secondary prevention patients) and whose triglycerides are less than 150 mg/dL to remain on simvastatin but be taken off gemfibrozil with no alternative therapy. Fish oil supplementation is given as an alternative to patients with LDL at goal and triglycerides of 150-249 mg/dL. Niacin is given to patients with LDL at goal and triglycerides of 250-499 mg/dL. Patients whose LDL is not at goal receive an increased dose of simvastatin (20 or 40 mg), and those with a history of pancreatitis or triglycerides of 500 mg/dL or greater are kept on gemfibrozil but converted to rosuvastatin (Crestor, AstraZeneca)

HF READMISSIONS continued from page 8

within 30 days of discharge with those readmitted after 30 days or not at all. Presenting the results at the ASHP meeting, Blair Kaplan, PharmD, BCPS, and Clare Bergman, PharmD, BCPS, inpatient clinical pharmacists at the VA medical center, reported that earlier and more frequent readmissions were more common among patients who received oral diuretic therapy for less than 24 hours before discharge; who were not

or pravastatin (Pravachol, Bristol-Myers Squibb) at an equivalent or higher dose, as indicated by their LDL level. (Pravastatin and rosuvastatin are less likely to interact with gemfibrozil.) “We wanted to outline [the algorithm] for the physicians to make it as easy as possible so they would have to make as few benchmark decisions as possible,” said Molly Haselden, PharmD. In doing so, patients “wouldn’t get lost under the radar or get an inappropriate combination.” The protocol also stresses individualized care, added Thomas J. Worrall, PharmD, BCPS, an ambulatory care clinical pharmacy specialist at RHJ VAMC. The physician and patient work together to come up with the best plan based on history and risk factors, he said. “Anytime a medication is changed for lipids or cholesterol, we always monitor it and make additional changes if needed.” A study of the new algorithm’s effect on a subset of patients, presented by Dr. Haselden and her colleagues at the ASHP meeting, showed a statistically but not clinically significant change in pre- and post-intervention triglycerides (107.5 vs. 159.5 mg/dL; P<0.001) and LDL (81.2 vs. 75.0 mg/dL; P=0.01) among 81 patients whose LDL and triglyceride levels were at goal (150 mg/dL or lower) when they were removed from gemfibrozil in response to the FDA contraindication. The increase in triglycerides “was not clinically significant, as additional therapy would not be added for a triglyceride level of 159 mg/dL,” said Dr. Worrall. An additional eight patients whose LDL levels were not at goal at baseline had a significant increase in triglycerides post-intervention (107.6 vs. 156.1 mg/dL; P=0.01); mean LDL did not change significantly (119.6 vs. 119.1 mg/dL; P=0.82). Mean total cholesterol, high-density lipoprotein (HDL) and the ratio of aspartate aminotransferase to alanine aminotransferase did not change across the total group of 89 patients. Analyses of patients receiving alternative therapies such as fish oil or niacin, or different

statins with gemfibrozil, are under way. Another study presented at the meeting suggested that fish oil might offer an effective alternative to gemfibrozil. In a retrospective chart review of 248 patients on background simvastatin therapy, researchers identified 39 patients who were converted to fish oil supplementation from gemfibrozil during June to December 2011. Triglycerides and LDL decreased (12.5% and 16.7%, respectively) among these patients (mean age, 66.2 years), reported Christine Huber, PharmD, BCPS, a clinical pharmacy specialist in primary care, and Haley J. Morrill, PharmD, a resident at Providence VA Medical Center, in Providence, R.I. Although the findings were not significant, “it was surprising for us because normally you would expect the LDL to go up,” Dr. Huber said. All patients in the study received the over-the-counter fish oil supplied by the VA pharmacy. Most of the patients—27 of 39—were prescribed the recommended daily dose of 4,000 mg. “I was surprised that the primary care physicians had selected a recommended dose,” Dr. Huber said, adding that she expected the physicians would start with lower doses. Doses ranged from 1,000 to 4,000 mg. A subanalysis revealed that patients taking 4,000 mg daily achieved better triglyceride control, she said.

prescribed an ACEI or angiotensinreceptor blocker and a β-blocker at discharge; and who were not compliant with medications or follow-up care. Although the investigators noted that the rate of 30-day readmissions at the medical center was low, they acknowledged that the results “suggest that there is room for improvement.” Dr. Kaplan told Pharmacy Practice News, “We found that none of the patients who were readmitted during the study period of six months [had been] seen in the newly initiated heart failure

pharmacist clinic. This gives us hope that over time, more patients will have the opportunity to receive medication education and optimization to prevent future hospital readmissions.”

For Fish Oil, Rx Is Best? Robert DiDomenico, PharmD, a cardiovascular clinical pharmacist at the University of Illinois at Chicago College of Pharmacy, noted in an interview that prescription fish oil supplements (Lovaza omega-3-acid ethyl esters, Reliant Pharmaceuticals) may be preferable to over-the-counter products as an alternative to gemfibrozil because they are regulated by the FDA. “If you’re identifying a patient who clearly has hypertriglyceridemia or low HDL and you are purposely trying to raise HDL with one of these products, I might be more inclined to use a brand-name product,” he said. “The alternative is to use the over-the-coun-

Rural Health Care Approach These programs can be incorporated even at small rural hospitals, according to another study presented at the ASHP meeting. In the study, conducted at Eastern Maine Medical Center (EMMC), in Bangor, Maine, pharmacists played an integral role within an interdisciplinary

ter product and follow the patient closely, and iff you don’t see the t response you want, switch to the brand.” b Dr. DiDomeenico added that the current emphasis on taking patients off gemfibrozil and providing an alternative may be “the wrong side of the coin.” The focus may instead need to shift toward replacing simvastatin with another statin, he noted. Simvastatin’s availability as a generic has led to its widespread use, he said, but “are we focusing on the right drug to switch out?” He said a good candidate for such a switch is atorvastatin calcium (Lipitor, Pfizer). In addition to being a cost saver— the statin recently became available as a generic—it is slightly more potent than simvastatin and “doesn’t have as many of the hard-and-fast contraindications that simvastatin has.” C. Michael White, PharmD, a professor and the chair of the Department of Pharmacy Practice at the University of Connecticut, in Storrs, and the author of numerous papers on statins, has his own prescription for managing patients on the lipid-lowering medications—avoiding rash cessations of therapy. “A protocol that just takes someone with a high risk of pancreatitis due to high triglycerides off gemfibrozil would not be smart,” Dr. White said. Better therapeutic options, he noted, include keeping the patient on gemfibrozil but switching their statin to pravastatin or rosuvastatin, given the latter drug’s lower risk for interacting with gemfibrozil, or keeping the patient on simvastatin but using high-dose fish oil, niacin or fenofibrate (Tricor, Abbott Laboratories) instead of gemfibrozil. —Susan Birk Drs. Haselden, Worrall, Huber and White reported that they had no relevant ﬁnancial conﬂicts of interest. Dr. DiDomenico reported that he has served on Roche’s advisory board.

team that educated patients with HF and enhanced continuity of care, resulting in decreased readmission rates and improved reimbursement rates. To be compliant with CMS reimbursement requirements, EMMC, which has six affiliated primary care clinics, established a Heart Failure Readmission Reduction Team, consisting of physicians, pharmacists, nurses and administrators from inpatient and outpatient settings. The Pharmacy Department was responsible for educating patients

•

see HF READMISSIONS, page 22

12 Operations & Management

Pharmacy Practice News • January 2013

Compliance

Experts Offer Survey, Audit Survival Tips Chicago—Pharmacy leaders should plan ahead to ready their departments for an audit or survey by any of the several state and federal agencies that could come knocking on the door, recommended compliance experts at the 2012 leadership conference of the American Society of Health-System Pharmacists. “Being familiar with these organizations and understanding what your role is in the different types of audits and surveys is a requirement for pharmacy leadership,” said Patricia C. Kienle, MPA, BS Pharm, FASHP, the director of accreditation and medication safety for Cardinal Health Pharmacy Solutions, in Laflin, Pa. Karla M. Miller, PharmD, BCPP, the assistant vice president of pharmacy services and clinical therapeutics for the Hospital Corporation of America Clinical Services Group, in Nashville, Tenn, made a similar entreaty at the meeting. “At the heart of all of these organizations is good patient care and protection of patients,” but each has its own focus and ways of operating, Dr. Miller said in a breakout session on compliance survival strategies. “Be sure you know how to respond to these situations, even the ones that are out of your control.” In addition to surveys by the relatively familiar accreditation groups and the Centers for Medicare & Medicaid Services (CMS), pharmacy leaders could conceivably find themselves dealing with investigations by the Office of Inspector General, the Drug Enforcement Administration (DEA) or any of the state licensing boards for pharmacy and medicine. Dr. Miller said that on-site DEA inspections are on the rise. “Make sure executive leadership is aware of [the DEA representatives’] presence, get them a private room and a direct contact to

work with” and be prepared to provide the biannual inventory report, inventory records, theft and loss reports, policies for medication diversion prevention, substance abuse in the workplace and controlled substance monitoring, as well as other required documents, she said. “If you can get those [reports] in front of the DEA, you don’t have much to worry about. It’s when you don’t have these quickly in an orderly manner that they’re going to ask questions,” she said. CMS has its own areas of recent focus, including its newly implemented reimbursement penalties for excessive hospital readmissions ((Pharmacy Practice News, December, page 1). Ms. Kienle advised pharmacy leaders to prepare for CMS scrutiny by taking a deeper, closer look at the agency’s Conditions of Participation (CoP) (http://www.cms.gov/

Regulations-and-Guidance/Guidance/ Manuals/downloads/som107ap_a_hospitals.pdf ). For the three major health care accrediting groups in the United States— the Joint Commission, the American Osteopathic Association (AOA) and Det Norske Veritas (DNV)—the foundation of their standards is the CoP. Organizations also need to familiarize themselves with the CoP because “CMS is taking a more global approach to what happens in hospitals,” including looking more closely at how the CoP feeds in to the accreditation process, Ms. Kienle said in an interview. Medication-related sections affecting pharmacists are spread throughout the document, not just in the 17 CoP for Pharmaceutical Services. “It’s up to you to know where they are,” added Ms. Kienle, who has served on the Pharmacotherapy Specialty Council of the

Planning Select

Store

Monitor

Order

Administer

Dispense

Evaluation Figure. Medication use system.

Hospital Professional and Technical Advisory Committee of the Joint Commission. “The first half [of the CoP] is almost all about restraints. The second half is all about the operations of the hospital, and the pharmaceutical services piece is key there,” Ms. Kienle said. “There are other things that directly affect our medication perspective, particularly on the acute care side, that are in other areas [of the CoP] as well. So I would suggest you look at that link and make sure you have it available to you.” She added, “Our responsibility in our enterprise is a bigger net than what we do in the pharmacy. We need to get that message out loud and clear … and sometimes we need to use some of these federal standards as support for what we want to do in our organizations.”

Storing Medications Is Potential Trouble Spot Standards in the CoP for storage, for example, have changed from requiring that all drugs be locked to requiring that all drugs and biologics be secured and locked when necessary. That change has “put a big onus on the hospital to define what they think is secure,” Ms. Kienle said. “So these are things that should be in your policies. … Do you have a policy that says who has access to medications in your organization? And it needs to be way bigger than pharmacy and nursing because there are lots of other people b who have access to specific carved-out areas of meds.” Ms. Kienle noted that 5% of hospitals receive a validation survey by CMS following an accreditation survey. “What they want to do from a validation standpoint is to make sure those accrediting organizations are complying with the

Tips for Boosting Compounding Safety

dhering to a few core strategies can go a long way toward improving the safety of your hospital’s partnerships with outside sterile compounders and in the process avoid compliance issues during site surveys, according to Patricia C. Kienle, MPA, BS Pharm, FASHP, the director of accreditation and medication safety for Cardinal Health Pharmacy Solutions, in Laflin, Pa.. She said that the following approaches could be particularly useful: • Ensure that any source used for the provision of medications meets your health system’s standards. “This isn’t limited to compounding pharmacies; any purchases outside of your known, acceptable vendors need to be vetted.” • Review the contract you have with any compounding pharmacy (both sterile and nonsterile). • Read the ASHP Guidelines on Outsourcing Sterile Compounding Services (www.ashp.org/ DocLibrary/Bestpractices/MgmtGdlOutsourcingSterileComp.aspx). • Assess your internal compliance with United States Pharmacopeia (USP) Chapter <797>. Accreditation

organizations often ask for the most recent gap analysis if a facility is not USP <797> compliant. Complete a new gap analysis if needed (both for nonhazardous as well as hazardous sterile compounding), and share the results with hospital leadership. As with many partnerships or alliances, it is crucial to review the documentation for any compounding pharmacy, Ms. Kienle noted. The following records can be particularly revealing and should be on your quality control checklist: • Pharmacy license in the state where the outsourced pharmacy is located. • DEA registration, if controlled substances are provided. • Registration with the FDA, as applicable and/ or accreditation by the Pharmacy Compounding Accreditation Board for sterile compounding (does not apply to radiopharmaceuticals). • Wholesaler or distributor license in the state where the outsourced pharmacy is located, if required. • If the outsourced pharmacy is located in another state, out-of-state wholesaler or distributor license,

if required by your state. • If the outsourced pharmacy is located in another state, any special license required by your state (e.g., controlled substances, sterile compounding), as applicable. • Licensure of pharmacists employed by the outsourced pharmacy. • Registration/certification of pharmacy technicians employed by the outsourced pharmacy, if applicable. • Written training program that meets USP <797> requirements and any state requirements, if applicable. • Summary of results of personnel competence. • Quality monitoring, including sterility testing of each batch and pyrogen testing if nonsterile ingredients are used. • Sources of ingredients. • Product recall procedures and records. • Proof of liability insurance. • Records of regulatory inspections. —S.B.

Operations & Management 13

Pharmacy Practice News • January 2013

Compliance federal standards,” she said. For that reason, “they don’t survey against [the Joint Commission] or AOA or DNV standards, they survey against the CoP.” The vast majority of accreditation standards overlap with those of CMS, she said, “but there are some subtle differences or different approaches,” and pharmacists need to know what those are. According to Ms. Kienle, hospital and health-system pharmacists can expect heightened scrutiny in the wake of the recent fungal meningitis outbreak (related article, page 1). “You’ve got to believe

when these folks are coming in to survey now and in the near future that this compounding issue is going to come up loud and clear,” she said. “The responsibility from a federal perspective is [to ensure] that patients are safe, as it should be. With the atrocious situation that’s occurring with compounding, I think we’re going to see more and more questions in that area.” The high level of public trust phar-

macists have enjoyed for decades has been tarnished, at least temporarily, by a disaster “that never should have occurred,” she said. In Gallup public opinion surveys, pharmacists have ranked among the top three most trusted groups of professionals for the past nine years. “I’m betting we’re not going to be there this year,” she said. To prepare for survey questions focused

on compounding (sidebar), pharmacists should ensure that the need for a compounded preparation is clinically appropriate, she advised. “Some compounds have been used based on convenience or the lack of standardization of concentrations in some organizations. Now is the time to assess the appropriateness and evidence-based practices. Organizations that have been unable to standardize [based on physician preference] can now approach this issue with a different level of urgency.” —Susan Birk

EX-AP-0020-201111 EX-AP-0039-201201

14 Clinical

Pharmacy Practice News • January 2013

Critical Care

PHARM COST continued from page 7

demonstration of how even in these [challenging economic] times, new programs like this can be initiated to help improve patient care at the hospital.”

Study Limitations Christopher J. Edwards, PharmD, BCPS, a clinical staff pharmacist in emergency medicine at the University of Arizona Medical Center–University Campus, in Tucson, pointed to

postsurgical pain control for u s e d i v p to 7 pro e s 2 ho o d urs * e On

EXPAREL is the only single-dose local analgesic that… • Provides up to 72 hours1* of analgesia with • Reduced opioid requirements1† • Without the need for catheters or pumps

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

Important Safety Information: EXPAREL is contraindicated in obstetrical paracervical block anesthesia. EXPAREL has not been studied for use in patients younger than 18 years of age. Non-bupivacaine-based local anesthetics, including lidocaine, may cause an immediate release of bupivacaine from EXPAREL if administered together locally. The administration of EXPAREL may follow the administration of lidocaine after a delay of 20 minutes or more. Other formulations of bupivacaine should not be administered within 96 hours following administration of EXPAREL. Monitoring of cardiovascular and neurological status, as well as vital signs should be performed during and after injection of EXPAREL as with other local anesthetic products. Because amide-type local anesthetics, such as bupivacaine, are metabolized by the liver, EXPAREL should be used cautiously in patients with hepatic disease. Patients with severe hepatic disease, because of their inability to metabolize local anesthetics normally, are at a greater risk of developing toxic plasma concentrations. In clinical trials, the most common adverse reactions (incidence ≥10%) following EXPAREL administration were nausea, constipation, and vomiting. *Pivotal studies have demonstrated the safety and efficacy of EXPAREL in patients undergoing bunionectomy or hemorrhoidectomy procedures; additional studies are underway to further demonstrate the safety and efficacy in other procedures. † The clinical benefit of the attendant decrease in opioid consumption was not demonstrated. Reference: 1. Gorfine SR, Onel E, Patou G, et al. Bupivacaine Extended-Release Liposome Injection for Prolonged Postsurgical Analgesia in Patients Undergoing Hemorrhoidectomy: A Multicenter, Randomized, Double-blind, Placebo-controlled Trial. Dis Colon Rectum. Dec 2011;54(12):1552-1559.

Please see brief summary of Prescribing Information on back page.

some shortcomings in the FSMH study. “Reallocation of inpatient staff to the [ED] may not be applicable to all hospitals,” Dr. Edwards said. “Pharmacists working in an [ED] should ideally have specialized training.” Additionally, “I would have liked to see a breakdown of hard versus soft money. They didn’t differentiate. Soft money is not as impressive as hard when trying to persuade administrators.” However, Dr. Edwards said he considers the study “interesting because it describes a smaller community hospital—17 beds in the emergency department. Most of the literature comes from large teaching hospitals.”

‘Reallocation of inpatient staff to the [ED] may not be applicable to all hospitals; pharmacists working in an [ED] should ideally have specialized training.’ —Christopher J. Edwards, PharmD, BCPS He also gave kudos to the researchers for their thorough approach to documentation. “The paper stresses the importance of documentation to present to the administration to justify the cost,” he said. “Documentation, documentation, documentation. Getting your foot in the door is the hardest part.” He added, “You have to present and make a case. The tighter the budget, the more difficult it will be [to convince hospital administrators].” For FSMH, there are indications that those budget pressures may be lifting, in part due to more recent successes with their ED pharmacy initiative. “In the article, we mentioned approval for 4.5 FTE technicians and these positions are currently in the process of being filled,” Dr. Nana said. “Overall, the hours have been expanded to 20 hours of coverage a day, seven days a week from our initial six hours of coverage, five days a week. In addition, due to the positive results seen, a sister hospital, Franciscan St. Margaret Health–Dyer, has also initiated an ED pharmacy program at their site.” —George Ochoa

For more information, visit www.EXPAREL.com Drs. Nana and Edwards reported no relevant ﬁnancial conﬂicts of interest.

Operations & Management 15

Pharmacy Practice News • January 2013

Practice Pearl

Pharmacists Help With CMS Core Measure Adherence Lindsay I. Varga, PharmD, BCPS Clinical Pharmacy Specialist in Internal Medicine

Elizabeth Marino Sabo, PharmD, BCPS Clinical Pharmacy Specialist in Infectious Disease

Jacqueline M. von Vital, PharmD, BCPS Clinical Pharmacy Specialist in Anticoagulation

Suzanne Y. Brown, MS, RPh Director of Pharmacy Services Pennsylvania Hospital Philadelphia, Pennsylvania

ore measures (CMs) are a set of evidence-based quality indicators created by the Centers for Medicare & Medicaid Services (CMS) and the Joint Commission. They have been shown to reduce the risk for complications, prevent recurrences, and otherwise promote optimal treatment of patients presenting with specific conditions. Failure to comply with the CMs may result in decreased reimbursement. At Pennsylvania Hospital, we saw an opportunity to leverage a unit-based clinical pharmacist model to help achieve and sustain CM compliance goals. Pharmacist involvement enabled the hospital to improve compliance in all the medication-related CMs that were targeted, with 100% compliance in a majority of the measures.

Implementation Plan The Department of Pharmacy Services saw an opportunity to use its established unit-based clinical pharmacist model to help achieve and sustain CM compliance goals. Together with the hospital’s Quality Management Department, they identi-

fied 9 medication-related CMs as opportunities for pharmacist involvement (Table 1). In March 2011, the hospital’s Pharmacy and Therapeutics Committee approved the new pharmacy-initiated program. Before the program’s launch in April 2011, an education plan was developed for pharmacists and house staff. Pharmacists were educated on the areas covered in the CM initiative—acute myocardial infarction (AMI), heart failure (HF), and pneumonia (PN)—and were given an introduction to CMs. House staff were educated about CMs and the potential of pharmacy to help the hospital achieve compliance goals. In November 2011, when stroke was added to the hospital’s CM dashboard, education related to stroke therapeutics was provided to the house staff. Pharmacy realigned its workflow model to accommodate the new responsibilities. Unit-based clinical pharmacists identified patients with an “admitting diagnosis” of AMI, HF, PN, or stroke every weekday via an emailed list from clinical data analysts. They also screened patients for CM diagnoses during daily patient care rounds. Pharmacists assessed medication-related CM compliance using patient-specific worksheets created by the pharmacy clinical specialists in internal medicine, infectious disease, and anticoagulation (Figure). After the unit-based clinical pharmacists evaluated the patients and discussed them with the multidisciplinary team, they determined which of 3 actions were required, and they proceeded accordingly (Table 2). Clinical pharmacists maintained patient review worksheets to facilitate communication between covering pharmacists, and after discharge the worksheets served as monitoring tools to

Table 1. Targeted Medication-Related Core Measures (as of August 2012) Measure Set

Measure ID No.

Measure Short Name

Acute myocardial infarction (AMI)

AMI-2

Aspirin prescribed at discharge

AMI-3

ACEI or ARB for LVSD

AMI-5

β-Blocker prescribed at discharge

AMI-10

Statin prescribed at discharge

Heart failure (HF)

HF-3

ACEI or ARB for LVSD

Pneumonia (PN)

PN-6

Initial antibiotic selection

Stroke (STK)

STK-1

Venous thromboembolism prophylaxis

STK-2

Discharged on antithrombotic therapy

STK-6

Discharged on statin

ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; LVSD, left ventricular systolic dysfunction Based on reference 1.

Figure. Portion of a patient-specific core measure worksheet for acute myocardial infarction. assess monthly pharmacy interventions and trends. In December 2011, after 8 months of this paper process, the Pharmacy Department implemented a computerized pharmacy clinical surveillance program, Pharmacy One Source Sentri7. This program interfaced with the hospital’s electronic charting system and computerized provider order entry system to extract relevant clinical patient data related to CM areas. With this data, the Pharmacy Department built and generated rules-based report lists. These lists identified patients with specific admitting diagnoses who were not ordered an appropriate medication (eg, “AMI diagnosis without appropriate meds”). The pharmacy created similar lists for each CM set. Electronic clinical surveillance streamlined the screening process and created a more efficient workflow for the pharmacists. The interface with the hospital’s electronic medication administration record system provided faster real-time patient identification. Pharmacists also documented interventions directly into the surveillance program and added notes to communicate with other pharmacists in the department.

Monitoring of Process The hospital’s quality management team monitored and reported CM compliance monthly at a Core Measures

Task Force meeting. The Pharmacy Department also monitored and reported the following data at each meeting: • Number of patients reviewed by the pharmacists • Number of documentations made in the patient medical record by pharmacists • Number of recommendations to the provider • Provider acceptance rate of recommendations made by pharmacists During the first 17 months of the pharmacy-based initiative, pharmacists reviewed 2,742 patients, made 218 documentations in patient charts, and made 224 recommendations, with an acceptance rate of 96%. With the addition of pharmacy involvement, the hospital was able to improve compliance in the 9 targeted medication-related CMs, with 100% compliance in a majority of the measures.

Keys to Success Due to the success of the pharmacy CM program, we believe that the same type of service could be replicated at other organizations. The group efforts of the Department of Pharmacy, the Department of Quality and Patient Safety, the performance improvement leadership, and clinical data analysts provided an optimal interdisciplinary platform for success. Institutions

•

see COMPLIANCE, page 16

16 Operations & Management

Pharmacy Practice News • January 2013

Practice Pearl

COMPLIANCE should consider several factors to optimally replicate the program.

for CM assessment. The Department of Quality and Patient Safety reviews compliance rates on a monthly basis and shares patient cases with the Pharmacy Department.

Departmental Partnerships

Staff Education

An integral aspect of this project is the relationship of the Pharmacy Department with the Department of Quality and Patient Safety and performance improvement leadership. Working together allows us to share ideas and optimally identify patients who are appropriate

Education on pathophysiology and therapeutics of disease states, as well as on the background of CMs, is vital in preparing unit-based clinical pharmacists to become contributing members of the health care team in assessing CM compliance.

continued from page 15

Table 2. Actions Required After Compliance Assessment Compliance Level

Action Required

Patient compliant with all medication CMs

No action needed

Patient noncompliant with medication CMs due to contraindication

Document contraindication in permanent medical record

Patient noncompliant with medication CMs and no contraindication identified

Communicate with provider and recommend compliance

CM, core measure

Workflow and Accountability This project was integrated into our department’s operational structure,

which includes unit-based clinical pharmacists who are deployed on the floors and closely interact with the patients, nurses, dieticians, and providers on a daily basis. The unit-based clinical pharmacists are held accountable for completing the CM checklists and communicating information to the rest of the health care team.

Standardized Clinical Surveillance Process Whether a paper or electronic process is used, the establishment of a consistent method for identifying and evaluating patients is integral to success.

Interdisciplinary Patient Care Rounds ... to receive the monthly e-newsletter from

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

The unit-based clinical pharmacist is a member of an interdisciplinary team that meets daily during patient care rounds. During these rounds, valuable information about the patient is presented that allows the team to screen patients using the CM checklists and identify those who would benefit from pharmacy intervention. Without this coordinated effort among the disciplines, the screening process would be much more challenging.

Ongoing Monitoring And Feedback Compliance rates and intervention data are gathered and reviewed each month at a Core Measures Task Force meeting. This data also is shared with the unit-based clinical pharmacists and house staff. The pharmacy CM program is dynamic, and pharmacists’ suggestions to improve the program are encouraged and integrated into the program.

Conclusion Based on our experience at Pennsylvania Hospital, we feel that a unit-based clinical pharmacist model can be leveraged to support a hospital in achieving CM compliance. Success in such a program is best achieved with interdisciplinary partnership, staff education, and standardization, as well as ongoing monitoring and feedback.

References

1. Centers for Disease Control & Prevention and The Joint Commission. Specifications Manual for National Hospital Inpatient Quality Measures. Version 4.0. January 2012.

Operations & Management 17

Pharmacy Practice News • January 2013

Finance

SAVINGS

Part 1 of a Two-Part Series

continued from page 1

According to Carlos Marin, RPh, lead pharmacist in the IV room of the Oncology Department at Overlook, the initiative began when the Finance Department approached the pharmacy and asked it to track discarded infliximab (Remicade, Janssen). “Every time, we were able to capture payment for a certain percentage of the waste if we documented it,” he explained. In a pilot study, Mr. Marin and his colleagues identified 11 drugs stocked in single-dose vials at the hospital’s outpatient infusion center and documented any amounts that went unused; they had the same success that they’d seen with wasted infliximab. The targeted drugs are mainly monoclonal antibodies and chemotherapeutic agents, and the pharmacists responsible for order entry in specific areas were trained on how to document wasted portions of every vial. To make the process easy and fast, the pharmacy’s orderentry system prompts users to record the amount of unused portions of all of the relevant drugs. The system won’t let pharmacists proceed until they supply the requested information, and the extra steps add only a few seconds to the process, according to Mr. Marin. The results were eye-opening: In 2011, reimbursements for drug waste for the 11 drugs totaled nearly $508,000. Oxaliplatin and bevacizumab (Avastin, Genentech) accounted for 70% of that total. From January to August 2012, the hospital recouped another $346,515. That amount included waste reimbursement for several drugs administered mostly in the inpatient setting, and accounted for about $8,000 over a two-month period. “You won’t get full payment for all of the unused portion of a vial, but you will get a percentage of these very expensive drugs and realize income that otherwise would not have been there,” Mr. Marin said. For example, the hospital submitted $491,000 worth of claims to CMS for wasted bevacizumab, but received $191,724 in reimbursement. Since the pilot study, the list of drugs scrutinized for waste reimbursement has expanded to more than 30 agents. “We try to capture those very expensive drugs [for which] reimbursement is very beneficial for the hospital, and it’s working out very well,” Mr. Marin said.

uating the use of pancreatic enzyme therapy and adjusting (even eliminating) therapy when appropriate. By the end of the initiative, Dr. Downer calculated an overall annual cost avoidance of $92,000 for their facility—a mean of about $2,050 per patient. After the local pharmacy service noticed that the average cost of enzyme therapy for its facility exceeded costs at comparable VA facilities nationally, the

Pharmacy and Therapeutics Committee approved a pharmacist telephone clinic to evaluate therapy for patients prescribed more than 60,000 lipase units daily. Between Sept. 1, 2011 and April 1, 2012, 45 patients received clinical pharmacist intervention. “I called each patient and worked with them to see if we could get them on an appropriate dose,” Dr. Downer said. “I tried to find a way to reduce their daily

pill burden and still control their disease, and, ultimately, [reduce] the total cost of the prescribed medication.” Dr. Downer performed a thorough medical chart review and interviewed each patient for any current or past symptoms of pancreatic disease. She evaluated patients for the frequency and consistency of their bowel movements, any history of weight loss and currently prescribed proton pump inhibitors. “First, I wanted to gauge how they were doing with their current treatment,” she said. If

•

see SAVINGS, page 18

Targeting Pancreatic Enzyme Therapy At the Ralph H. Johnson VA Medical Center in Charleston, S.C., Karen C. Downer, PharmD, and her first-year pharmacy residency program director, Dorothy E. Jenrette, PharmD, saw an opportunity to simultaneously reduce costs and improve patient care by eval-

BEYOND ABOVE-AND-BEYOND

18 Operations & Management

Pharmacy Practice News • January 2013

Finance

continued from page 17

the patients were symptom-free, enzyme doses were gradually lowered by one capsule per meal until they reached a personalized dose without having symptoms. Many patients were able to decrease their doses significantly and keep symptoms under control. Patients whose symptoms were unstable were referred to the gastroenterology clinic. All patients received routine follow-up to assess for symptom changes. “I continued to call them until we got them on the lowest dose that kept them stabilized,” Dr. Downer said. Pill burden was decreased from 6.5 to 2.1 capsules per day ((P=0.0001) for the entire group, and from 7.9 to 5.5 for patients who remained on therapy after the intervention. In some cases, even patients with confirmed pancreatitis were weaned completely off the enzymes because they remained asymptomatic without therapy. Twenty-eight patients (62%) were able to discontinue therapy completely; 10 (22%) had a dose reduction; and seven (16%) remained on their original dose. The mean daily dose change from 105,444 to 79,111 lipase units daily represented a statistically significant difference for patients who continued therapy (n=17). Perhaps the most surprising finding was that 25 of the patients had no history of chronic pancreatic disease and were able to discontinue therapy completely. These patients often were taking enzymes for a history of a single acute pancreatic attack or other bowel disorders for which enzyme therapy was providing no benefit. Based on those outcomes, the facility was able to establish criteria for prescribing pancreatic enzyme therapy, which includes a confirmed diagnosis of chronic pancreatic disease from a gastrointestinal specialist or by radiographic findings, and patient symptoms of fat malabsorption evidenced by steatorrhea or weight loss. “The diagnosis should not come from a primary care physician or after one visit to the ED [emergency department] without expert or radiographic confirmation,” Dr. Downer said. “The prescription also goes through the pharmacy for approval based on these criteria. These enzymes have become high-cost medications that we monitor monthly to evaluate for appropriate prescribing and use.”

Pharmacists Do It Cheaper Than PBMs By assuming responsibility for pharmacy services normally delegated to its external pharmacy benefit management (PBM) company, one major hospital system created a novel and more cost-effective way to provide pharmacy

benefits for employees enrolled in the system’s health plan. “Traditionally, we’ve outsourced most of our pharmacy benefit management work,” said Kelley Curtis, PharmD, MBA, corporate director of pharmacy at Sisters of Charity of Leavenworth Health System (SCLHS), in Lenexa, Kan. “Our approach has changed, and now we’ve become very involved with pharmacy benefit consulting and development to create our own pharmacy benefit plan that covers

per day in the fourth quarter of 2011 (before the plan was brought in house) to $71.35 and $67.94 in the subsequent two quarters (after the plan was internalized) (Figure). Other measures that contributed to savings included encouraging prescribers to select medications in accordance with evidence-based practice, monitoring employee drug usage for over- and underutilization and using copay incentives to drive employees to use outpatient pharmacy services in hospitals where they are available.

100 82.89

‘The [HR] department at many hospitals doesn’t realize [it has] access to ... a high level of pharmacy benefits specialists right in their own backyard.’ —Kelly Curtis, PharmD

Cost (dollars)

SAVINGS

71.35

67.94 60 40 20 0

Preimplementation (Q4 2011)

our health system employees and their beneficiaries.” The health system is composed of 11 SCLHS and Exempla Healthcare facilities in four states, and the employee health plan covers more than 19,000 individuals. In 2010, the health system spent more than $15 million on prescription medications for its employees, including $7 million for mail order prescriptions. SCLHS/Exempla met with inpatient pharmacy leadership and asked them to identify options that would provide pharmacy benefits to employees, potentially improving health outcomes and lowering drug costs. For example, according to Dr. Curtis, pharmacy administrators worked with the health system’s mail order pharmacy to replace all employee prescriptions supplied by the external PBM with drugs purchased at considerable savings with group purchasing organization (GPO) prices. “Usually you have to pay what [the insurer] wants, but we were able to replace the inventory with prescriptions purchased under GPO pricing, since our employees are eligible for ‘own-use’ pricing,” she said. The health system also internalized specialty pharmacy services. Dr. Curtis explained that specialty pharmacy services had been outsourced to a company that did little to help SCLHS/Exempla employees enroll in prescription assistance programs. Many were left to scramble for resources to obtain expensive medications, so the health system shifted the responsibility to its own retail infusion center pharmacy, which staffs specialty pharmacy experts. That change alone resulted in a $400,000 savings, along with a notable rise in the number of employees enrolled in prescription assistance programs. The specialty pharmacy plan cost per day of therapy also dropped considerably: from $82.89

As of September 2012, the system had saved an annualized $1,875,000 before drug rebates—a 13.4% decrease from the previous year. “We’ve handed over many decisions about our employees’ pharmacy care to some of our hospital pharmacy leaders,” Dr. Curtis said. “The human resources department at many hospitals doesn’t realize [it has] access to such a high level of pharmacy benefits specialists right in their own backyard.” For other systems that want to follow the SCLHS/Exempla lead, Dr. Curtis said the pharmacy department should inform human resources personnel that it wants to become involved with the development of an employee pharmacy plan. “Hospital pharmacy leadership tends to shy away from [such plans], but we could get a lot more involved. We have thousands of employees and their families who could benefit from our services.”

Savings From Lean Process Improvement Significant savings also accrued to the University of Massachusetts Memorial Medical Center, in Worcester, as a result of its Pharmacy Department’s participation in a system-wide lean process improvement initiative and concurrent adjustments to medication management protocols. By changing its approach to dispensing and administering costly oncology drugs, the facility racked up savings of more than $400,000 from fiscal year (FY) 2009-2010 to FY 2010-2011, according to Karen Smethers, PharmD, BCOP, the manager of the Oncology Pharmacy and Investigational Drug Services. The cost for inpatient rituximab (Rituxan, Genentech) alone decreased from baseline by more than $250,000 in FY10 and by $150,000 in FY11. The driving force behind the savings was shifting the location of the infusion from

Postimplementation (Q1 2012)

(Q2 2012)

Figure. Cost per day, specialty pharmacy benefit.

the inpatient setting to the outpatient clinic, where the cost of delivering care is lower and reimbursement is higher, Dr. Smethers noted. The lean process improvement effort was made possible through the work of various multidisciplinary committees representing pharmacists, physicians, nurses, clerical staff, laboratory personnel and hospital administrators, Dr. Smethers added. As a result of that collaboration, several additional costcutting strategies were recommended by the medical center’s Oncology Pharmacy and Therapeutics Subcommittee and carried out by caregivers. The strategies included the following: • Promoting evidence-based provision of care so that patients receive only those oncology drugs determined to be effective for their specific circumstances according to the most current research. For example, the pharmacy promoted the use of oral immunosuppressive therapy, such as mycophenolate and tacrolimus in clinically stable patients, to reduce cost and promote earlier discharge. • Ensuring that patients arrive at the oncology clinic only after they have received prior authorization from their insurance company. • Encouraging prescribers to practice dose rounding within 5%, which eliminates waste from partially used vials. —Steve Frandzel Drs. Smethers, Downer and Curtis, and Mr. Martin reported no relevant ﬁnancial conﬂicts of interest.

Policy 19

Pharmacy Practice News • January 2013

Sterile Compounding

NECC CRISIS continued from page 1

by Iowa but located outside its borders. “We’re moving full bore ahead,” Carmen Catizone, MS, RPh, DPh, the executive director of the association, told Pharmacy Practice News. “The response from the states has been incredible. They’ve said, ‘This is an issue we own and we’re going to move quickly on it.’” Preliminary findings from the inspections suggest that the New England Compounding Center (NECC), whose tainted methylprednisolone was the source of the meningitis outbreak, is by no means the only pharmacy to compound drugs that are seldom if ever tied to a specific prescription. Four of the six compounders were found to distribute non-patient-specific, preservative-free sterile injectables, which can be at odds with “traditional” compounding—that is, the preparation of medications prescribed in small quantities for specific individuals. Two of the pharmacies produced very large volumes of non-patient specific sterile drugs, Dr. Catizone reported. The findings have been sent to Iowa, he said, and the state “is going to be making some determinations.” Dr. Catizone praised Iowa’s “innovative” initiative. “They were able to think outside the box and say, ‘We can’t hire staff to do this, but we have the funding and we can use it in a way that gets the outcomes accomplished.’” He said other states were weighing similar agreements with NABP. The NABP approach—to preserve individual states’ ownership of traditional pharmacy compounding oversight while broadening their ability to monitor nonresident compounders who ship product into their states—appears to cross over into FDA turf, which is oversight of interstate-shipped medications. The FDA, meanwhile, is pressing Congress for new legislation that will reinforce the agency’s hand in policing practices that go beyond prescriptiondriven compounding. But some pharmacy sources worry that the FDA’s push for new authority may threaten states’ traditional role and raise the risk for a possible “federalization” of compounding practice. “I am absolutely terrified that the FDA is going to get in the middle of this, and more importantly, I’m more afraid that Congress is going to get into the middle of this and they’re going to muck this thing up,” said Eric Kastango, RPh, MBA, the president and the CEO of Clinical IQ, speaking at the American Society of Health-System Pharmacists’ Midyear Clinical Meeting last month. Others have raised doubts about whether a budget-minded Congress would allocate funds that the FDA needs to hire more inspectors and expand its national oversight of compounders. The FDA has moved to ease these concerns. In Decem-

ber, agency officials met with pharmacy and health department regulators from all 50 states to solicit input on how federal and state agencies might work together to “close gaps” in the “regulatory framework,” as Margaret Hamburg, MD, the FDA Commissioner, put it. Pharmacy board officials who spoke at the two-hour FDA public hearing that followed their early meetings at the agency’s headquarters in Silver Spring, Md., expressed confidence in their capacity to regulate compounding pharmacies in their own states, but some said that

they were challenged by the difficulty of controlling nonresident compounders. “We know what happens in pharmacies in Arkansas,” said John Clay Kirtley, PharmD, the executive director of the Arkansas State Board of Pharmacy. “We don’t necessarily know about what is happening in specific pharmacies in other states that ship into our state.” Several board officials noted that insufficient funding often hampers states’ regulatory efforts. Jay Campbell, RPh, JD, the executive director of the North Carolina Board of Pharmacy, said that where-

as his board and others in the Southeast region generally have the resources to carry out their missions, others around the country “are dealing with revenue challenges.” He said it was important for state lawmakers to recognize that pharmacy boards must be adequately funded “and not simply be viewed as a revenue stream” for general purposes. Despite concerns about the potential for federal encroachment on what traditionally has been state regulatory terrain, some board officials saw areas where

•

see NECC CRISIS, page 20

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20 Policy

Pharmacy Practice News • January 2013

Sterile Compounding

NECC CRISIS continued from page 19

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federal and state collaboration might prevent future public health calamities like the one caused by NECC. Cody Wiberg, PharmD, MS, RPh, the executive director of the Minnesota Board of Pharmacy, suggested that “joint investigations” by the FDA and state boards might be a way to ensure better enforcement of federal and state compounding standards. In most states, he said, pharmacy boards “are regulatory licensing agencies. We’re not law enforcement agencies. We can’t initiate criminal proceedings; the FDA can. In some of these really horrible situations, [that may] get the attention of folks even more” than separate actions by federal or state regulators alone, he noted. At the federal level, Senate and House committees have launched investigations into the causes of the NECC disaster, laying the groundwork for legislative remedies later in 2013. At least two bills have been introduced in the House. The one gaining the most attention was initiated by Rep. Edward J. Markey (D-Mass.), in whose district NECC’s manufacturing facility is located. Under the bill, most compounding pharmacies that engage in mass production would be regulated by the FDA as drug manufacturers.

ASHP’s Initial Take on Bills The impact that the Markey bill or other legislative proposals might have on hospital pharmacy was a key point of focus during a late-breaking session at the ASHP’s Midyear Clinical Meeting, titled “A Compounding Tragedy—A National Response.” Joseph Hill, ASHP’s director of federal legislative affairs, said that although the Markey bill seems to provide the FDA with regulatory flexibility, the “core issue” is how to define the point on the continuum of compounding practice where state jurisdiction ends and federal authority kicks in. He said that it was “not so simple” to write legislation that clarifies the definitions of “compounding considered to be under state jurisdiction versus mass production—what people are calling manufacturing but may be potentially a third category.” Mr. Hill emphasized that ASHP had not yet made any policy determinations. “We want to make sure that when we do go down the road of addressing any regulatory gaps, we don’t have a kneejerk reaction” and “we’re not cutting off absolutely necessary practices going on in the health systems.” One such necessary practice that concerns ASHP is anticipatory compounding—the preparation of sterile solutions in advance not for specific patients but based on known usage patterns—for example in a hospital operating room. Mr. Hill said the language in the Markey bill seems to define compounding “a bit

more narrowly” when it limits the practice to being “pursuant to a patient prescription” and leaves out the phrase “or in anticipation of a prescription.” If that definition were included in any final legislation, Mr. Hill said, anticipatory compounding “would not be automatically subject to state regulation,” with the possibility that it could come under FDA purview. However, he noted that the bill does grant the FDA some flexibility to issue waivers to entities to perform certain compounding activities, “such as in anticipation of a patient prescription.” Addressing the issue of federal versus state jurisdiction, Christopher J. Topoleski, director of federal regulatory affairs at ASHP, said that it might be “useful for the FDA and state boards to collaborate further to identify entities that may be massproducing and show they are licensed properly and to share information about enforcement actions or disciplinary procedures” not just between themselves but also with the general public. Mr. Topoleski noted that the agency had asked to be given “full authority to collect test samples of compounded products and ... records in compounding pharmacies, such as prescriptions received, volume of operations and product test results.” He said ASHP was concerned “this new authority would essentially federalize regulation of traditional pharmacy compounding. We believe that this should remain within the jurisdiction of state boards of pharmacy.” He also said that the FDA “quite frankly does not have the capacity to inspect all compounding pharmacies. Agency collaboration with state boards will be necessary to identify entities engaged in these activities.” Mr. Hill said that it was vital for ASHP to continue “talking to Congress as well as other stakeholders to ensure that we’re moving forward.” From a lobbyist’s perspective, he added, “one of the things we say a lot is ‘You want to be on the train rather than under it.’”

Who Is To Blame? As for who is to blame for the NECC disaster, Dr. Catizone said it’s easy to point fingers. However, “every single one of us was responsible for this tragedy,” he stressed. “The regulatory system broke down, the pharmacy compounding system broke down, [and] the collaboration between FDA and the states broke down.” Because methylprednisolone purchasers failed to exercise due diligence, he added, “those transactions [also] broke down.” In terms of next steps, Dr. Catizone cautioned again focusing too much on the nuances of regulatory policy. “We can’t argue [over the definition of compounding versus manufacturing] for 20 more years,” he said. “Too many patients have been killed. We have to act.” —Bruce and Joan Buckley

Policy 21

Pharmacy Practice News • January 2013

Reimbursement Matters

It’s Time To Take Charge! A

s health care reform moves forward, all pharmacists need to understand how payment mechanisms for outpatient services are determined. Why not just leave this task to your billing and coding team or to some administrative person in your department? One compelling factor is the system that the Centers for Medicare & Medicaid Services (CMS) uses to determine payments. CMS bases its policies primarily on how your staff decides to choose and use a medication—and the degree to which your staff accurately documents those treatment decisions. Moreover, new payment mechanisms are built on a platform of data from previous years. So if your systems and records are less than stellar, you’ll be contributing to a new program that underestimates true costs of care. For these reasons, it should be clear that reimbursement issues are everyone’s responsibility. So let’s look at 2013 and see if we can find opportunities to improve your involvement in your hospital or health system’s reimbursement practices. In this article, we’ll focus on the recently released outpatient prospective payment system (OPPS) rules that cover the medical benefit that applies to Part B drugs used by Medicare patients and that often serve as a base for decisions made by other payors (http:// www.gpo.gov/fdsys/pkg/FR-2012-11-15/ pdf/2012-26902.pdf ). (The rules won’t cover Part D medications handled under the Pharmacy Benefit, nor do they apply to self-administered drugs.) First, it is important to understand exactly who can be deemed an outpatient. Basically, an outpatient is anyone who is not admitted to the facility as an inpa-

New Drugs Not Yet Assigned Unique HCPCS Code

tient, regardless of where in the facility the person is being treated. This includes the emergency room, the operating room for ambulatory surgery patients, ancillary treatment areas such as the gastrointestinal lab, catheterization lab, radi-

ology, outpatient clinics or the infusion center. (Sound familiar? These sites are some of the same places covered by 340B pricing in eligible facilities.) The next step is to understand the correct type of codes to use. In a world

Table 1. A Sampling of Drugs & Biologicals for Which Pass-Through Status Expired Dec. 31, 2012 (abbreviated to drugs only) CY2013 HCPCS

CY 2013 Long Descriptor

CY 2013 SI

CY 2013 APC

C9275

Injection, hexaminolevulinate hydrochloride, 100 mg, per study dose

N/A

J0221

Injection, alglucosidase alfa (Lumizyme), 1 mg

1413

J0588

Injection, incobotulinumtoxin A, 1 unit

9278

J0597

Inject, C–1 Esterase inhibitor (human) Berinert 10 units

9269

J0775

Injection, collagenase clostridium histolyticum, 0.01 mg

1340

J0840

Inject, Crotalidae polyvalent immune fab (ovine), up to 1 g

9274

J0897

Injection, denosumab, 1 mg

9272

J1290

Injection, ecallantide, 1 mg

9263

J1557

Injection, immune globulin (Gammaplex), intravenous, non-lyophilized (e.g., liquid), 500 mg

9270

J1741

Injection, ibuprofen, 100 mg (code change from C9279)

N/A

J3095

Injection, telavancin, 10 mg

9258

J3262

Injection, tocilizumab, 1 mg

9624

J3357

Injection, ustekinumab, 1 mg

9261

APC, ambulatory payment classification; CY, calendar year; HCPCS, health care common procedure coding system

New Pass-Through Drugs

Specified Covered Outpatient Drugs (SCODs) Costing >$80/Day

Lower-Cost Packaged Products Costing <$80/Day

Figure. OPPS 2013: Drugs and Biologicals Paid in One of Four Ways. ASP, average sales price; AWP, average wholesale price; HCPCS, health care common procedure coding system; OPPS, outpatient prospective payment system; WAC, wholesale acquisition cost

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

Bonnie Kirschenbaum, MS, FASHP

of electronic transactions, there are two types of codes—those assigned to products, known as health care common procedure coding system (HCPCS) codes, and those used for services (current procedural terminology, or CPT codes). Both types are used to transmit the details of the patient visit to the payor. Using the wrong codes or relying on miscellaneous codes results in little to no payment and may trigger an audit; hence the need for accuracy in all of your coding efforts. Here’s a particularly important caveat to keep in mind: Although most HCPCS codes are listed generically, a few are unique to the brand name, including IVIG products, as well as these examples: • Q2048 – Doxil brand of liposomal doxorubicin (billing unit 10 mg): Effective July 1, 2012 • Q2049 – Lipodox brand of liposomal doxorubicin (billing unit 10 mg): Effective July 1, 2012 • J7315 – Mitosol brand of mitomycin ophthalmic: Effective Jan. 1, 2013

The CMS Approach To Reimbursement CMS pays for Part B drugs in one of four ways (Figure). CMS recognizes that new drugs coming to market are very expensive and if they choose to cover them, reimbursement is slightly higher for these “pass-through” drugs for two to three years, as shown in the two left columns. Mainstream products that are separately payable are in the third column and those that have been on the market for some time and may be generically available fall into the fourth column. (In tha latter group, the products are often low-cost items and are thus bundled into the patient visit rather than being separately reimbursed.) Additionally, two different sets of rules determine payment rates for drugs used in a hospital facility and those in a physician office setting. Although both are based on average sales price (ASP), the mark-up has differed over the years that the model has been in place. This year marks the first time that the payment rates will be identical in both care settings and paid at ASP plus 6%—a 2% increase over 2012 for hospital outpatient medications. ASP is the average selling price of manufacturers’ sales of all U.S. purchases for each national drug

•

see TAKE CHARGE!, page 22

22 Policy

Pharmacy Practice News • January 2013

Reimbursement Matters

TAKE CHARGE! continued from page 21

code (NDC) for one calendar quarter, divided by the total number of units sold in that quarter. It excludes nominal pricing and Medicaid “best price,” and for 2013 continues to exclude 340B pricing. It also includes volume and prompt pay discounts, free goods, chargebacks and rebates. It is updated quarterly, so be sure to get on the distribution list (http:// www.CMS.gov/McrPartBDrugAvgSalesP rice/01a172012ASPFiles.asp).

A Few More Important Details The four columns in the Figure (page 21) outline several key reimbursement points that need to be heeded: Pay attention to pass-through status. CMS carefully determines which drugs are deserving of pass-though status, changes this list at least annually and adds to it during the year as new products come to market. Newly released products may have temporary HCPCS codes (usually starting with C) that change to permanent codes (usually starting with J). Look closely at Federal Register Tables (excerpted in Tables 1 and 2) to see the changes effective Jan. 1, 2013 and ensure that these updates have been made to the drug master files on your pharmacy’s computer system and to the hospital’s charge description master. Don’t leave this very important step to someone else to take care of! Use billing units correctly. CMS reimburses for the actual doses of the drug administered, not for the whole vial of the drug. The concept of using billing units was introduced several years ago and there’s little tolerance for facilities that haven’t yet figured out how to implement the simple mathematical requirements. Essentially every Part B drug that CMS pays for has a billing unit assigned to it (listed in the quar-

HF READMISSIONS continued from page 11

and establishing a screening criterion to better target patients with HF. Patients were targeted if they were on the cardiac telemetry unit, had a left ventricular ejection fraction less than or equal to 40% and had a primary care provider (PCP) within an affiliated provider group. “We focused on the worst of the worst patients, those most likely to come back repeatedly,” said lead researcher Dmitri Cohen, PharmD, BCPS, currently a critical care resident at the University Medical Center of Southern Nevada, in Las Vegas. “Before the study, they were getting very little education. During the study, we’d spend 30 minutes to an hour with each patient having detailed conversations.” During each session,

terly ASP tables) Divide the dose administered by the billing unit assigned to get the number of billing units that can be billed for and round up to the next whole billing unit as needed. If you bill for too few units, you’re underpaid. If you bill for too many you’re overpaid and in eitheßr case will fail an audit. Example: Drug A comes in a 1,000-mg vial and has a 100-mg billing unit. If the dose is 600-mg, bill for six billing units of 100 mg. If the dose is 650 mg, bill for seven billing units of 100 mg. Bill for drug waste. This is possible if certain conditions are met. Ask yourself the following four questions and proceed to billing for waste only if the answers to all four questions are “yes,” following the guidelines set up by the Medicare Administrative Contractor (MAC) range you’re in: Q: Is the drug being used for a Medicare patient being treated in an outpatient area? Q: Am I using a single-dose vial of the drug? Q: Does the product have a HCPCS code? Q: Does the dose fall into the passthrough or separately payable category (not the <$80 per day bundle noted in the Figure)? Bundled payments. This payment strategy comes into play with drugs that cost (determined by ASP) less than $80 per day, an increase from $75 in 2012. These are not separately reimbursable but instead are bundled into the payment the facility receives for the patient visit. CMS assumes that the facility finance team can tease out which portion of the bundle goes to which department within the facility. How are you getting your part of the bundle? Equally important, are you actually reporting the use of these products even though they are not separately reimbursable? If not, you are short-changing the amount that the bun-

patients were encouraged to take their blood pressure and weight on a daily basis and to notify their PCP of any significant changes. After the sessions, pharmacists emailed notes and suggestions to the PCP’s nurse case manager and pharmacist. The initiative was implemented on Sept. 26, 2011. The team found that 30-day HF readmission rates fell significantly after implementation, from 17.6% to 19.5% before implementation (20082011 data) to 11.7% after (data from first three quarters of 2012), a 33% to 40% reduction ((P=0.0327). The special challenges of serving a rural area affected the study, noted Dr. Cohen. “It was a very unhealthy population of patients. For many of them, exercise was chopping wood once a week,” he said. “They hadn’t been edu-

Table 2. A Sampling of Drugs and Biologicals With Pass-Through Status in CY 2013 (abbreviated to drugs only) CY2012 HCPCS Code

CY2013 HCPCS Code

CY 2012 Long Descriptor

Final CY 2013 SI

Final CY 2013 APC

C9285

Lidocaine 70 mg/tetracaine 70 mg, per patch

9285

C9286

J0485

Injection, belatacept, 1 mg

9286

C9287

J9042

Injection, brentuximab vedotin, 1 mg

9287

C9288

J0716

Injection, centruroides (scorpion) immune f(ab)2 (Equine), 1 vial

9288

C9289

J9019

Injection, asparaginase Erwinia chrysanthemi, 1,000 IU

9289

C9290

Injection, bupivicaine liposome, 1 mg

9290

C9292

Injection, pertuzumab, 10 mg

9292

C9293

Injection, glucarpidase, 10 units

9293

N/A

C9294

Injection, taliglucerase alfa, 100 units

9294

N/A

C9295

Injection, carfilzomib, 1 mg

9295

N/A

C9296

Injection, ziv-aflibercept, 1 mg

9296

J0131

Injection, acetaminophen, 10 mg

9283

APC, ambulatory payment classification; CY, calendar year; HCPCS, health care common procedure coding system

dle payment is worth. Worse still, you’re losing the drug administration fee for the product because these fees are paid only when the product is billed for as well. Drug Administration Fees. This vital part of reimbursement experienced a rise in all 2013 fees except one. Check out the fee tables to ensure that you’re using the correct CPT codes and that you’ve set up documentation mechanisms either electronically or manually to ensure that all necessary data is being captured. Also, make sure that your pharmacy department is being paid for drug preparation and handling. (Again, those payments need to be teased out of the drug administration fee bundle.)

More Tasks To Tackle

cated. They didn’t know the symptoms of heart failure, so they were waiting too long before coming in.”

loss on a single day or 5 pounds in a week, and treated at that point, their chances for success would be much better.” These studies illustrate the need for pharmacists to play a more crucial role as hospitals become more responsible for reducing readmission rates, Dr. White noted. He predicted that finding clinical care and reimbursement models “that integrate all health care providers who add value to the team in a manner that best utilizes their skills and time availability” is going to be a core feature of a successful system.

Patients’ Role Is Crucial Getting patients to understand their medications, to be committed to taking them as prescribed, to weighing themselves and to taking their blood pressure daily is a huge step forward, according to C. Michael White, PharmD, the department head and a professor in the Department of Pharmacy Practice at the University of Connecticut in Storrs. “The addition of the safety measures is vitally important and new in this study,” he said. “The patients we see with 20 pounds of fluid overload are at greatest risk for intubation, nosocomial infections, arrhythmias and death. If they were caught with more than 2 pounds of weight

Here’s a few additional reimbursement-related tasks that you or someone in your department should be championing: regular charge master reviews; periodic audits of patient bills/claims; development of printed order sheets; embedding billing information in computerized prescriber order entry systems; reviewing claim denials/write-offs; participating in pre-RAC (recovery audit contractor) or RAC audits and appeals; and commenting on proposed CMS rules. Good luck with meeting these reimbursement challenges in 2013 and beyond!

—Dana Hawkins-Simons, with additional reporting by Sarah Tilyou Drs. Page, Trevarrow, Moye, Groo, Kaplan, Bergman, Cohen and White reported no relevant ﬁnancial conﬂicts of interest.

SAMSCAÂ® (tolvaptan) tablets for oral use %ULHI 6XPPDU\ RI 3UHVFULELQJ ,QIRUPDWLRQ )RU FRPSOHWH SUHVFULELQJ LQIRUPDWLRQ FRQVXOW RIÂ¿FLDO SDFNDJH LQVHUW \ J J J WARNING: INITIATE AND RE-INITIATE IN A HOSPITAL AND MONITOR SERUM SODIUM SAMSCA should be initiated and re-initiated in patients only in a hospital where serum sodium can be monitored closely. Too rapid correction of hyponatremia (e.g., >12 mEq/L/24 hours) can cause osmotic demyelination resulting in dysarthria, mutism, dysphagia, lethargy, affective changes, spastic quadriparesis, seizures, coma and death. In susceptible patients, including those with severe malnutrition, alcoholism or advanced liver disease, slower rates of correction may be advisable. INDICATIONS AND USAGE: 6$06&$ LV LQGLFDWHG IRU WKH WUHDWPHQW RI FOLQLFDOO\ VLJQLÂ¿FDQW K\SHUYROHPLF DQG HXYROHPLF K\SRQDWUHPLD VHUXP VRGLXP P(T / RU OHVV PDUNHG K\SRQDWUHPLD WKDW LV V\PSWRPDWLF DQG KDV UHVLVWHG FRUUHFWLRQ ZLWK Ã€XLG UHVWULFWLRQ LQFOXGLQJ SDWLHQWV ZLWK KHDUW IDLOXUH FLUUKRVLV DQG 6\QGURPH RI ,QDSSURSULDWH $QWLGLXUHWLF +RUPRQH 6,$'+ Important Limitations 3DWLHQWV UHTXLULQJ LQWHUYHQWLRQ WR UDLVH VHUXP VRGLXP XUJHQWO\ WR SUHYHQW RU WR WUHDW VHULRXV QHXURORJLFDO V\PSWRPV VKRXOG QRW EH WUHDWHG ZLWK 6$06&$ ,W KDV QRW EHHQ HVWDEOLVKHG WKDW UDLVLQJ VHUXP VRGLXP ZLWK 6$06&$ SURYLGHV D V\PSWRPDWLF EHQHÂ¿W WR SDWLHQWV CONTRAINDICATIONS: 6$06&$ LV FRQWUDLQGLFDWHG LQ WKH IROORZLQJ FRQGLWLRQV Urgent need to raise serum sodium acutely: SAMSCA has not been studied in a setting of urgent need to raise serum sodium acutely. Inability of the patient to sense or appropriately respond to thirst: 3DWLHQWV ZKR DUH XQDEOH WR DXWR UHJXODWH Ã€XLG EDODQFH DUH DW VXEVWDQWLDOO\ LQFUHDVHG ULVN RI LQFXUULQJ DQ RYHUO\ UDSLG FRUUHFWLRQ RI VHUXP VRGLXP K\SHUQDWUHPLD DQG K\SRYROHPLD Hypovolemic hyponatremia: 5LVNV DVVRFLDWHG ZLWK ZRUVHQLQJ K\SRYROHPLD LQFOXGLQJ FRPSOLFDWLRQV VXFK DV K\SRWHQVLRQ DQG UHQDO IDLOXUH RXWZHLJK SRVVLEOH EHQHÂ¿WV Concomitant use of strong CYP 3A inhibitors: .HWRFRQD]ROH PJ DGPLQLVWHUHG ZLWK WROYDSWDQ LQFUHDVHG WROYDSWDQ H[SRVXUH E\ IROG /DUJHU GRVHV ZRXOG EH H[SHFWHG WR SURGXFH ODUJHU LQFUHDVHV LQ WROYDSWDQ H[SRVXUH 7KHUH LV QRW DGHTXDWH H[SHULHQFH WR GHÂ¿QH WKH GRVH DGMXVWPHQW WKDW ZRXOG EH QHHGHG WR DOORZ VDIH XVH RI WROYDSWDQ ZLWK VWURQJ &<3 $ LQKLELWRUV VXFK DV FODULWKURP\FLQ NHWRFRQD]ROH LWUDFRQD]ROH ULWRQDYLU LQGLQDYLU QHOÂ¿QDYLU VDTXLQDYLU QHID]RGRQH DQG WHOLWKURP\FLQ Anuric patients: ,Q SDWLHQWV XQDEOH WR PDNH XULQH QR FOLQLFDO EHQHÂ¿W FDQ EH H[SHFWHG WARNINGS AND PRECAUTIONS: Too Rapid Correction of Serum Sodium Can Cause Serious Neurologic Sequelae (see BOXED WARNING): Osmotic GHP\HOLQDWLRQ V\QGURPH LV D ULVN DVVRFLDWHG ZLWK WRR UDSLG FRUUHFWLRQ RI K\SRQDWUHPLD H J ! 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Co-administration with Hypertonic Saline: 7KHUH LV QR H[SHULHQFH ZLWK FRQFRPLWDQW XVH RI 6$06&$ DQG K\SHUWRQLF VDOLQH &RQFRPLWDQW XVH ZLWK K\SHUWRQLF VDOLQH LV QRW UHFRPPHQGHG Drug Interactions: Other Drugs Affecting Exposure to Tolvaptan: CYP 3A Inhibitors: 7ROYDSWDQ LV D VXEVWUDWH RI &<3 $ &<3 $ LQKLELWRUV FDQ OHDG WR D PDUNHG LQFUHDVH LQ WROYDSWDQ concentrations [see Dosage and Administration (2.3), Drug Interactions (7.1)] 'R QRW XVH 6$06&$ ZLWK VWURQJ LQKLELWRUV RI &<3 $ [see Contraindications (4.4)] DQG DYRLG FRQFRPLWDQW XVH ZLWK PRGHUDWH &<3 $ LQKLELWRUV CYP 3A Inducers: $YRLG FR DGPLQLVWUDWLRQ RI &<3 $ LQGXFHUV H J ULIDPSLQ ULIDEXWLQ ULIDSHQWLQ EDUELWXUDWHV SKHQ\WRLQ FDUEDPD]HSLQH 6W -RKQÂ¶V :RUW ZLWK 6$06&$ DV WKLV FDQ OHDG WR D UHGXFWLRQ LQ WKH SODVPD FRQFHQWUDWLRQ RI WROYDSWDQ DQG GHFUHDVHG HIIHFWLYHQHVV RI 6$06&$ WUHDWPHQW ,I FR DGPLQLVWHUHG ZLWK &<3 $ LQGXFHUV WKH GRVH RI 6$06&$ PD\ QHHG WR EH increased [see Dosage and Administration (2.3), Drug Interactions (7.1)]. 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LQ WROYDSWDQ WUHDWHG SDWLHQWV 7DEOH OLVWV WKH DGYHUVH UHDFWLRQV UHSRUWHG LQ WROYDSWDQ WUHDWHG SDWLHQWV ZLWK K\SRQDWUHPLD VHUXP VRGLXP P(T / DQG DW D UDWH DW OHDVW JUHDWHU WKDQ SODFHER WUHDWHG SDWLHQWV LQ WZR GD\ GRXEOH EOLQG SODFHER FRQWUROOHG WULDOV ,Q WKHVH VWXGLHV SDWLHQWV ZHUH H[SRVHG WR WROYDSWDQ VWDUWLQJ GRVH PJ WLWUDWHG WR DQG PJ DV QHHGHG WR UDLVH VHUXP VRGLXP $GYHUVH HYHQWV UHVXOWLQJ LQ GHDWK LQ WKHVH WULDOV ZHUH LQ WROYDSWDQ WUHDWHG SDWLHQWV DQG LQ SODFHER WUHDWHG SDWLHQWV Table 1. Adverse Reactions (>2% more than placebo) in Tolvaptan-Treated Patients in Double-Blind, Placebo-Controlled Hyponatremia Trials System Organ Class MedDRA Preferred Term

Tolvaptan 15 mg/day-60 mg/day (N = 223) n (%) ( )

Placebo (N = 220) n (%)

Gastrointestinal Disorders 'U\ PRXWK

Constipation

General Disorders and Administration Site Conditions a 7KLUVW

Asthenia

Pyrexia

Metabolism and Nutrition Disorders b +\SHUJO\FHPLD

Anorexia c Renal and Urinary Disorders

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DRUG INTERACTIONS: Effects of Drugs on Tolvaptan: Ketoconazole and Other Strong CYP 3A Inhibitors: 6$06&$ LV PHWDEROL]HG SULPDULO\ E\ &<3 $ .HWRFRQD]ROH LV D VWURQJ LQKLELWRU RI &<3 $ DQG DOVR DQ LQKLELWRU RI 3 JS &R DGPLQLVWUDWLRQ RI 6$06&$ DQG NHWRFRQD]ROH PJ GDLO\ UHVXOWV LQ D IROG LQFUHDVH LQ H[SRVXUH WR WROYDSWDQ &R DGPLQLVWUDWLRQ RI 6$06&$ ZLWK PJ NHWRFRQD]ROH GDLO\ RU ZLWK RWKHU VWURQJ &<3 $ LQKLELWRUV H J FODULWKURP\FLQ LWUDFRQD]ROH WHOLWKURP\FLQ VDTXLQDYLU QHOÂ¿QDYLU ULWRQDYLU DQG QHID]RGRQH DW WKH KLJKHVW ODEHOHG GRVH ZRXOG EH H[SHFWHG WR FDXVH DQ HYHQ JUHDWHU LQFUHDVH LQ WROYDSWDQ H[SRVXUH 7KXV 6$06&$ DQG VWURQJ &<3 $ LQKLELWRUV VKRXOG QRW EH FR DGPLQLVWHUHG [see Dosage and Administration (2.3) and Contraindications (4.4)]. Moderate CYP 3A Inhibitors: 7KH LPSDFW RI PRGHUDWH &<3 $ LQKLELWRUV H J HU\WKURP\FLQ Ã€XFRQD]ROH DSUHSLWDQW GLOWLD]HP DQG YHUDSDPLO RQ WKH H[SRVXUH WR FR DGPLQLVWHUHG WROYDSWDQ KDV QRW EHHQ DVVHVVHG $ VXEVWDQWLDO LQFUHDVH LQ WKH H[SRVXUH WR WROYDSWDQ ZRXOG EH H[SHFWHG ZKHQ 6$06&$ LV FR DGPLQLVWHUHG ZLWK PRGHUDWH &<3 $ LQKLELWRUV &R DGPLQLVWUDWLRQ RI 6$06&$ ZLWK PRGHUDWH &<3 $ LQKLELWRUV VKRXOG WKHUHIRUH JHQHUDOO\ EH DYRLGHG [see Dosage and Administration (2.3) and Warnings and Precautions (5.5)]. Grapefruit Juice: &R DGPLQLVWUDWLRQ RI JUDSHIUXLW MXLFH DQG 6$06&$ UHVXOWV LQ D IROG LQFUHDVH LQ H[SRVXUH WR WROYDSWDQ [see Dose and Administration (2.3) and Warnings and Precautions (5.5)]. P-gp Inhibitors: 5HGXFWLRQ LQ WKH GRVH RI 6$06&$ PD\ EH UHTXLUHG LQ SDWLHQWV FRQFRPLWDQWO\ WUHDWHG ZLWK 3 JS LQKLELWRUV VXFK DV H J F\FORVSRULQH EDVHG RQ FOLQLFDO UHVSRQVH [see Dose and Administration (2.3) and Warnings and Precautions (5.5)]. 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Concomitant Medication: $GYLVH SDWLHQWV WR LQIRUP WKHLU SK\VLFLDQ LI WKH\ DUH WDNLQJ RU SODQ WR WDNH DQ\ SUHVFULSWLRQ RU RYHU WKH U counter drugs since there is a potential for interactions. Strong and Moderate CYP 3A inhibitors and Pg-p inhibitors: $GYLVH SDWLHQWV WR LQIRUP WKHLU SK\VLFLDQ LI WKH\ XVH VWURQJ H J NHWRFRQD]ROH LWUDFRQD]ROH FODULWKURP\FLQ WHOLWKURP\FLQ QHOÂ¿QDYLU VDTXLQDYLU LQGLQDYLU ULWRQDYLU RU PRGHUDWH &<3 $ LQKLELWRUV H J DSUHSLWDQW HU\WKURP\FLQ GLOWLD]HP YHUDSDPLO Ã€XFRQD]RO RU 3 JS LQKLELWRUV H J F\FORVSRULQH [see Dosage and Administration (2.3), Contraindications (4.4), Warnings and Precautions (5.5) and Drug Interactions (7.1)]. Nursing: $GYLVH SDWLHQWV QRW WR EUHDVWIHHG DQ LQIDQW LI WKH\ DUH WDNLQJ 6$06&$ >VHH 8VH ,Q 6SHFLÂ¿F 3RSXODWLRQV @ )RU PRUH LQIRUPDWLRQ DERXW 6$06&$ FDOO RU JR WR ZZZ VDPVFD FRP 0DQXIDFWXUHG E\ 2WVXND 3KDUPDFHXWLFDO &R /WG 7RN\R -DSDQ 'LVWULEXWHG DQG PDUNHWHG E\ 2WVXND $PHULFD 3KDUPDFHXWLFDO ,QF 5RFNYLOOH 0' SAMSCA is a registered trademark of Otsuka Pharmaceutical Co., Ltd., Tokyo, 101-8535 Japan

UNMET NEED. FILL IT.

FREE VVATER V2

CLEARANCE

Order SAMSCA® (tolvaptan)

15 mg

30 mg

NDC: 59148-020-50

NDC: 59148-021-50

Unique oral treatment for clinically significant hypervolemic and euvolemic hyponatremia

100 %

of physicians surveyed (N=57) would recommend SAMSCA to a colleague 1 In this same survey (patient cases; N=150), physicians were satisﬁed or very satisﬁed with SAMSCA 90% of the time1

Indication and important limitations • SAMSCA is indicated for the treatment of clinically significant hypervolemic and euvolemic hyponatremia (serum sodium <125 mEq/L or less marked hyponatremia that is symptomatic and has resisted correction with fluid restriction), including patients with heart failure, cirrhosis, and Syndrome of Inappropriate Antidiuretic Hormone (SIADH) • Patients requiring intervention to raise serum sodium urgently to prevent or to treat serious neurological symptoms should not be treated with SAMSCA. It has not been established that raising serum sodium with SAMSCA provides a symptomatic benefit to patients

Important safety information SAMSCA should be initiated and re-initiated in patients only in a hospital where serum sodium can be monitored closely. Too rapid correction of hyponatremia (e.g., >12 mEq/L/24 hours) can cause osmotic demyelination resulting in dysarthria, mutism, dysphagia, lethargy, affective changes, spastic quadriparesis, seizures, coma and death. In susceptible patients, including those with severe malnutrition, alcoholism or advanced liver disease, slower rates of correction may be advisable. Contraindications: Urgent need to raise serum sodium acutely, inability of the patient to sense or appropriately respond to thirst, hypovolemic hyponatremia, concomitant use of strong CYP 3A inhibitors, anuric patients. • Subjects with SIADH or very low baseline serum sodium concentrations may be at greater risk for too-rapid correction of serum sodium. In patients receiving SAMSCA who develop too rapid a rise in serum sodium or develop neurologic sequelae, discontinue or interrupt treatment with SAMSCA and consider administration of hypotonic fluid. Fluid restriction should generally be avoided during the first 24 hours • Dehydration and hypovolemia can occur, especially in potentially volume-depleted patients receiving diuretics or those who are fluid restricted. In patients who develop medically significant signs or symptoms of hypovolemia, discontinuation is recommended • Gastrointestinal bleeding in patients with cirrhosis: Use in cirrhotic patients only when the need to treat outweighs this risk • Avoid use with: CYP 3A inhibitors and CYP 3A inducers. Reduced dose of SAMSCA may be needed if used with P-gp inhibitors • Co-administration with hypertonic saline is not recommended • Monitor serum potassium in patients with levels >5 mEq/L and in those receiving drugs known to increase serum potassium Commonly observed adverse reactions: (SAMSCA vs placebo) thirst (16% vs 5%), dry mouth (13% vs 4%), asthenia (9% vs 4%), constipation (7% vs 2%), pollakiuria or polyuria (11% vs 3%) and hyperglycemia (6% vs 1%). Reference: 1. Market Rx 2010.

For more information about SAMSCA, visit samsca.com or call 1-877-726-7220.

Please see Brief Summary of FULL PRESCRIBING INFORMATION, including Boxed WARNING, on the following page. Manufactured by Otsuka Pharmaceutical Co., Ltd., Tokyo, 101-8535 Japan. Distributed and marketed by Otsuka America Pharmaceutical, Inc., Rockville, MD 20850. Samsca is a registered trademark of Otsuka Pharmaceutical Co., Ltd., Tokyo, 101-8535 Japan.

March 2012

0712A-4220K

PRINTER-FRIENDLY VERSION AVAILABLE AT PHARMACYPRACTICENEWS.COM

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

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

This allows clinicians to match the best product to the patient based on clinical condition and comorbidities. New products have become available available, providing more treatment options. For example, Bivigam (Biotest), a 10% liquid product for intravenous use, was approved in December 2012 and is expected to be released in early 2013. Also, there are now 4 Ig products indicated for subcutaneous use: Gammagard Liquid (Baxter), Gammaked (Grifols), and Gamunex-C (Grifols) come in 10% concentrations and can be administered intravenously or subcutaneously (PID only), and Hizentra (CSL Behring) comes in a 20% concentration. It should be noted that dosing adjustments are required for all SC agents when converting from IV. Another area of change for Igs is the use of these products for various new indications. Two products, Gammaked and Gamunex-C, are approved for use in patients with chronic inflammatory demyelinating polyneuropathy (IV only). Gammagard Liquid is approved to treat multifocal motor neuropathy. A common question regarding Ig products relates to whether they all are the same. Although clinicians have considered all Ig products to have comparable efficacy, they are not pharmaceutically equivalent. It is imperative that Ig products not be interchanged without full consideration of the pharmaceutical differences. The reasons for switching products may be clinical in nature and related to tolerability; they may be fiscal and based on contracting issues; or they may be due to product availability. It is best

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

to consider product changes as if the patient is naive to Ig use, with increased monitoring and conservative infusion times. Whereas Tables 1 to 5 may help facilitate these decisions, it is important to understand the clinical impact of changing products. Although all of the products contain primarily IgG, trace amounts of other Igs—IgA and IgM—as well as widely different stabilizing agents, may affect tolerability. The differences in salt, sugar, and overall osmolarity of these products are particularly important when patients have various comorbidities, such as renal dysfunction, diabetes mellitus, vascular disease, or heart failure. Differences between lyophilized and liquid products may result in changes in product concentration and infusion rate, as well as tolerability. The tables may be helpful in providing optimal care for patients receiving Ig products. They should be used as a general guide to help determine the product that is best suited for a particular patient population. Because there is variation from batch to batch, the exact numbers represent averages of selected batches; any one batch of any Ig product may have ranges outside these average numbers. When comparing administration rates, clinicians need to keep in mind that each patient has a maximum tolerated rate. This rate is based on patient tolerability and may be different for each product. Ig must be administered slowly initially and titrated as tolerated. The rate should be adjusted based on comorbidities as well. The infusion should be slowed or stopped if adverse events (AEs) become evident during the infusion. (See the prescribing information for each agent for more information about AEs.)

P H A R M AC Y P R AC T I C E N E WS • JA N UA RY 2 0 1 3

Table 1. Therapeutic Considerations

FDAApproved Indications

IgG Subclass,c %

IgA Content

pH (after reconstitution)

Plasma Source

Halflife, db

Viral Inactivation/ Removal

Producta

Manufacturer

Bivigam

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

PID

≤200 mcg/mL

4.0-4.6

Cold ethanol fractionation, 35 nm virus filtration, SD

Carimune NF

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

ITP, PID

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

6.4-6.8

Plasmapheresis, US donors (>16,000)

pH 4.0/pepsin, nanofiltration, TSE removal

60.5

Flebogamma 5% DIF Flebogamma 10% DIF

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

PID

<3.2 mcg/mLc,d

5.6±0.1 (5%)d 5.5±0.1 (10%)d

US source IQPPcertified plasma from FDAregistered sites

4-week dosing: 32±5 (5%), 37±13 (10%)

Pasteurization (60°C, 10 h), SD, dual nanofiltration (35+20 nm), fraction I and II+III precipitation, 4% PEG precipitation, pH 4.0 treatment, TSE removal

66.6

Gammagard Liquid 10%

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

MMN, PID

37 mcg/mL

4.6-5.1

Plasma from FDA-registered sites

SD, low pH, nanofiltration

60.9

Gammagard S/D 5%

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

CLL, ITP, KD, PID

<2.2 mcg/mL, <1 mcg/mLe

6.4-7.2

Plasmapheresis, 10,000 donors

37.7±15

Gammaked

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

CIDP, ITP, PIDf

47±13 mcg/mLc,d

4.1c,d

US source IQPPcertified plasma from FDAregistered sites

pH 4.2, caprylate chromatography purified, TSE removal

62.8

Gammaplex

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

PID

<10 mcg/mL

4.8-5.1

Plasma from FDA-registered sites

41±14

SD, nanofiltration, terminal low pH incubation

Gamunex-C

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

CIDP, ITP, PIDf

47±13 mcg/mLc,d

4.1c,d

US source IQPPcertified plasma from FDAregistered sites

pH 4.2, caprylate chromatography purified, TSE removal

62.8

Hizentra 20%

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

PID

≤50 mcg/mL

4.6-5.2

Plasmapheresis, US donors

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

68.7

Octagam 5%

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

PID

≤200 mcg/mLg

5.1-6.0

US source and recovered plasma

Cold ethanol, SD, pH 4.0 incubation for 24 h at 37°C

Privigen 10%

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

ITP, PID

≤25 mcg/mL

4.6-5.0

Plasmapheresis, US donors (≥60,000)

36.6

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

67.8

Footnotes on page 7; Key on page 8.

Editor’s Note: Bivigam was approved in late December 2012, but at press time it was not yet available.

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

IgG1

Streptococcus pneumoniaec

Type 1

Type 3

Haemophilus influenzae Type Bc

Streptolysin Oc

CMV

HAV

HBV (Surface Antibody)c

Herpes Simplex Type 1c

Polio Type 2c

IgG2

IgG3

IgG4

Diphtheria Toxinc

30.2

6.6

2.8

3.6 IU/mL (NT)

313 (EIA)

180 (EIA)

1:60 (CF)

300 IU/mL (HAI)

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

1:348 (RIA)

1:64 (RIA)

1:128 (CF)

1:64 (NT)

28.5 (5%), 27.9 (10%)

2.7 (5%), 3.0 (10%)

2.2 (5%), 2.5 (10%)

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

15±1 mg/L (5%)

30±6 PEI units/mL (5%), 69±16 U/mL (10%)

21±4 IU/mL (5%)

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

32.1

2.1

4.0 units/mL (NT)

21.2 mcg/mL (EIA)

1:2,320 (EIA)

68 PEI units/ mL (EIA)

16.4 IU/mL (RIA)

≥0.20 IU/mL (EIA)

VZV: 32 units/mL (NT)

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

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

17.5 mcgAbN/ mL (EIA)

8.5 mcg/mL (EIA)

11 mcg/mL (EIA)

1,150 IU (HH)

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

1:267 (RIA)

820 mIU/mL (RIA)

1:1,000 (EIA)

1:305 (NT)

29.7

4.8

2.7

7±2 AU/mL

87.4±22.2 mcg/mL

26.1±7.7 mcg/mL

13.0±2.4 mcg/mL

16,846± 13,648 Todd units/mL

57 PEI units/mL

1:139

65±19 IU/g Ig

1:22± 0.35

2.2 IU/mL

2.3 mcg/mL

791 mcg/mL

185 IU/mL

431 U/mL

20 IU/mL

4.7 IU/mL

5,129 AU/mL

29.7

4.8

2.7

7±2 AU/mL

87.4±22.2 mcg/mL

26.1±7.7 mcg/mL

13.0±2.4 mcg/mL

16,846± 13,648 Todd units/mL

57 PEI units/mL

1:139

65±19 IU/g Ig

1:22± 0.35

26.6

2.7

≥2.5 IU/mL

≥1,000 IU/mL

≥0.4 IU/mL

5-30 IU/mL

600-800 IU/mL

33-40 IU/mL

21-25 IU/mL

51 IU/g

1:8,192

1:1601:320 (NT)

28.7

2.3

1.2

4.9 (3.8-7.3) IU/mL

36.1 (26.4-45.0) IU/mL

1,746 (1,3102,010) IU/mL

76.4 (51.2-116.8) IU/mL

5.3 (3.0-10.1) IU/mL

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

Table 2. Pharmaceutical Considerations

Product

Method of Preparation i

Available Dosing Forms

Form

Gamma Globulin, %

Monomers, %

Bivigam

Cohn-Oncley, cold ethanol fractionation, SD

Liquid

Carimune NF

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

Lyophilized

≥96

Flebogamma 5% DIF Flebogamma 10% DIF

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

Liquid

99.6±0.2 (5%),c,d 99.6±0.1 (10%)c,d

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

Gammagard Liquid

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

IV, SC

Liquid

≥98

≥95 monomers + dimers

Gammagard S/D 5%

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

Lyophilized

≥90

96.4

Gammaked

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

IV, SC (PID only)

Liquid

≥98

100 monomers + dimersc,d

Gammaplex

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

Liquid

>99

≥99 monomers + dimers

Gamunex-C

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

IV, SC (PID only)

Liquid

≥98

100 monomers + dimersc,d

Hizentra

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

Liquid

≥98

≥90 monomers + dimers

Octagam

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

Liquid

≥96

≥90 monomers + dimers

Privigen

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

Liquid

≥98

≥98 monomers + dimers

Footnotes on page 7; Key on page 8.

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

IgM Content

Albumin

PEG

Sodium Content

Stabilizer

Osmolality/Osmolarity

Shelf Lifeh

Reconstitution Time

Glycine

24 mo refrigerated

Not applicable (liquid solution)

Trace

0% water, 0.9% saline

5% sucrose

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

24 mo

Several minutes

<2 mcg/mL (5%), <6 mcg/mL (10%)

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

Not detectable

Trace (<3.2 mmol/L)

5% sorbitol (polyol)

327±4.5 mOsm/kg (5%)c,d 342±7.2 mOsm/kg (10%)c,d

24 mo RT

Not applicable (liquid solution)

Trace

Not detectable

Glycine

240-300 mOsm/kg

36 mo refrigerated; 12 mo RT

Not applicable (liquid solution)

Trace

<3 mg/mL

<2 mg/mL

0.85%

2% glucose

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

24 mo

<5 min at RT; >20 min if cold

Trace

<20 mcg/mL

Trace (<7 mEq/L)

Glycine

264±4 mOsm/kgc,d

36 mo refrigerated; 6 mo RT

Not applicable (liquid solution)

<0.02 mcg/mLk

30-50 mmol/L

Sorbitol, glycine

480 mOsm/kg

24 mo

Not applicable (liquid solution)

Trace

<20 mcg/mL

Trace (<7 mEq/L)

Glycine

264±4 mOsm/kgc,d

36 mo refrigerated; 6 mo RT

Not applicable (liquid solution)

Trace

≤2%

≤10 mmol/L

Proline

380 mOsm/kg

30 mo RT

Not applicable (liquid solution)

≤0.1 mg/mL

10% maltosel

310-380 mOsm/kg

24 mo RT or refrigerated

Not applicable (liquid solution)

3 mg/L

Trace

Proline

240-440 mOsm/kg

36 mo RT

Not applicable (liquid solution)

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

Table 3. Cost Considerations Producta

Supply

Storage

Distribution

Return Policy Warranty

Packaging or Labeling Enhancements

Bivigam

5, 10 g

2°C-8°C, 24 mo; do not freeze

Tamper-evident seal, label with integrated hanger, peel-off label, latex-free stopper

Carimune NF

3, 6, 12 g

≤30°C

Wholesaler or direct

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

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

Flebogamma 5% DIF Flebogamma 10% DIF

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

2°C-25°C, 24 mo; do not freeze

Wholesaler or direct from Grifols USA (888) GRIFOLS

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

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

Gammagard Liquid

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

2°C-8°C, 36 mo; ≤25°C, 12 mo

Wholesaler or direct

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

Gammagard S/D 5%

2.5, 5, 10 g

≤25°C; do not freeze

Wholesaler or direct

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

Gammaked

1, 2.5, 5, 10, 20 g

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

Wholesaler

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

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

Gammaplex

5, 10 g

2°C-25°C, 24 mo; do not freeze

Wholesaler

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

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

Gamunex-C

1, 2.5, 5, 10, 20 g

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

Wholesaler or direct

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

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

Hizentra

5, 10, 20 mL

≤25°C, 30 mo

Wholesaler or direct

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

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

Octagam

1, 2.5, 5, 10, 25 g

2°C-25°C, 24 mo; do not freeze

Wholesaler or direct

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

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

Privigen

5, 10, 20 g

≤25°C, 36 mo

Wholesaler or direct

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

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

Key on page 8.

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

Table 4. IVIG Administration Ratesm IVIGa

Initial Infusion Rate

Maintenance Infusion Rate

Maximum Infusion Raten

Bivigam

0.5 mg/kg/min

Increase by 0.8 mg/kg/min every 20 min if tolerated up to 6 mg/kg/min

6 mg/kg/min

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

Carimune NF

0.48 mL/kg/h

1-2 mL/kg/h

3 mL/kg/h

No filter required; compatible with NaCl, D5W; increased risk for renal and thrombotic adverse effectsp

Flebogamma 5% DIF Flebogamma 10% DIF

0.6 mL/kg/h

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

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

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

Gammagard Liquid

0.5 mL/kg/h for 30 min

4 mL/kg/h; increase gradually as tolerated

5 mL/kg/h

No filter required; compatible with D5W but not NaCl; patients at risk for renal dysfunction or thrombotic events should be gradually titrated up to a more conservative maximum rate <2 mL/kg/hp

Gammagard S/D 5%

0.5 mL/kg/h for 30 min

1-2 mL/kg/h; increase rate every 15 min as tolerated

4 mL/kg/h (5%), 8 mL/kg/h (10%)

15-micron filter required and supplied with administration set; compatible with sterile water

Gammaked

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

4.8 mL/kg/h

No filter required; avoid NaCl even in evacuated containers; administer at minimum infusion rate practical to patients >65 or at risk for renal or thrombotic eventsp

Gammaplex

0.6 mL/kg/h

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

4.8 mL/kg/h

15- to 20-micron in-line filter recommended; administer at minimum infusion rate practical to patients at risk for renal dysfunction or thrombotic eventsp

Gamunex-C

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

4.8 mL/kg/h

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

Octagam

0.6 mL/kg/h for 30 min

1.2 mL/kg/h for 30 min, then 2.4 mL/kg/h

<4 mL/kg/h

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

Privigen

0.3 mL/kg/h

As tolerated, up to maximum recommended rate

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

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

Commentso

FOOTNOTES a

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

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

Average of sample lots.

d e

Cohn-Oncley is the original method of cold ethanol fractionation; Kistler-Nitschmann is the speciﬁc cold ethanol fractionation method used by the manufacturer (CSL Behring).

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

Data on ﬁle at Grifols.

Data on ﬁle at Bio Products Laboratory.

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

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

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

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

Under appropriate storage conditions.

Some infusion rates were converted from

those listed in the prescribing information for consistency and reader convenience. n

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

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

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

Log reduction factor values obtained through prescribing information; most are available on respective websites.

Data on ﬁle at Octapharma.

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

Table 5. Log Reduction Factor Comparisonsq Enveloped Viruses HIV Producta

Models for HCV

Model for Large DNA

SBV

BVDV

PRV

Nonenveloped Virus

TSE (Prion)

Bivigam

>9.62

>7.11

>11.79

>8.65

4.0 (PPV)

Carimune NF

≥26

≥19

≥9

≥25

≥19 (BEV)

Flebogamma 5% DIF, 10% DIF

≥20.30

≥6.49

≥16.61

≥23.15

≥15.04 (PPV), ≥13.33 (EMCV)

≥11.64

Gammagard Liquid 10%

≥14.8

≥16.8

≥16.9

≥5.7 (HAV), ≥7.7 (EMCV), ≥5.1 (MMV)

Gammagard S/D 5%

≥18.3 (HIV-1), ≥5.7 (HIV-2)

≥5.1

≥6.2

≥12.3

≥8 (HAV)

Gammaked 10%

≥14

≥16.3

≥12.2

≥5.0 (HAV)

≥6.6

Gammaplex 5%

>12.9

>20.2

>11.7

>5.9 (HAV), >7.5 (EMCV)

Gamunex-C 10%

≥14

≥16.3

≥12.2

≥5.0 (HAV)

≥6.6

Hizentra 20%

≥16.0

≥11.8

≥17.7

≥9.6 (EMCV), ≥7.8 (MMV)

≥14.8

Octagam 5%

≥14.6

≥16.7

≥16.1

≥9.5 (MEV), ≥7.7 (PPV)

≥6.7r

Privigen 10%

≥16.0

≥11.8

≥17.7

≥9.6 (EMCV), ≥7.8 (MMV)

≥14.8

Footnotes on page 7.

KEY HCV

hepatitis C virus

information not available

BGMS blood glucose monitoring systems

HIV

human immunodeﬁciency virus

normal saline

BVDV bovine viral diarrhea virus

IgA

immune globulin A

PEG

polyethylene glycol

IgG

immune globulin G

prescribing information

IgM

immune globulin M

PID

primary immunodeﬁciency

IQPP

International Quality Plasma Program

BEV

CIDP

bovine enterovirus (RNA model)

chronic inﬂammatory demyelinating polyneuropathy

CLL

chronic lymphocytic leukemia

D5W

dextrose 5% in water

EMCV encephalomyocarditis virus (RNA model) FDA

Food and Drug Administration

GDH- glucose dehydrogenasePQQ pyrroloquinolone quinone GDO

glucose-dye-oxidoreductase

HAV

hepatitis A virus

ITP

idiopathic thrombocytopenic purpura

IVIG

intravenous immune globulin

Kawasaki disease

MEV

mouse encephalomyelitis virus

MMN

multifocal motor neuropathy

MMV

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

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

PRV

pseudorabies virus

RIA

radioimmunoassay

RSS

reduced space symbology

room temperature

SBV

Sindbis virus

solvent detergent

subcutaneous

UIN

unique identiﬁer number