The Pharmacist’s News Source
Volume 40 • Number 10 • October 2013
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in this issue UP FRONT
CDC: antibiotic resistance still on the rise; better stewardship efforts urged.
New guidelines issued for postexposure HIV prophylaxis. Malnutrition often overlooked in cancer care.
OPERATIONS & MGMT
Leadership in Action: setting up healthy boundaries for yourself and your staff.
In reimbursement, don’t let distractions lead to revenue loss. New labeling tightens use of opioids in chronic pain.
New IPPS Rule Keeps Focus On 30-Day Readmits
Doomsday for PharmD Grads Or Alarmist Over-Reaction? B
he Centers for Medicare & Medicaid Services (CMS) updated its payment policies and rates earlier this month under the Inpatient Prospective Payment System (IPPS), and some hospitals will take a financial hit as a result of the changes. But the update that seems to be triggering the most attention is CMS’s continuing push to bring down 30-day hospital readmission rates via the steepest payment cuts yet imposed under the initiative. CMS is reducing reimbursement rates by up to 2% for 2,225 hospitals beginning Oct. 1 (the beginning of fiscal year 2014) as part of a program designed under the Affordable Care Act (ACA) to curb readmission rates. In fiscal year 2013, the program withheld up to 1% of reimbursements for hospitals that had too many readmissions within 30 days of discharge because of heart attack, heart failure and pneumonia. Under the ACA, the penalty will rise to 3% by 2015 and
y 2018, 20% of new phaarmacy graduates will enter a job m market that has no positions for them, aaccording to a top education expert. However dire such a crisis may aappear, experts interviewed by Pha armacy Practice News disputed this find ding. In a commentary in the Am merican Journal of Pharmaceutical E Education ((AJPE 2013;77:90; doi: 10 0.5688/ ajpe77590), Daniel L. Brown, Ph harmD, the director of faculty development at the Center for Teaching Excellence, and a professor of pharmacy practice at th he Lloyd L. Gregory School of Pharmaccy, Palm Beach Atlantic University, in West Paalm Beach, Fla., based his bleak jobs forecastt on an analysis of trends in pharmacy em mployment and pharmacy education. In 200 01, “the pharmacy academy began a period of un nprecedented growth, fueled by a long-standing shortage of pharmacists and an outstanding job market for new pharmacy graduates,” Dr. Brown wrote. New w colleges and schools of pharmacy opened, and existing programs expanded. As a result, the number of new PharmD graduates is expected to reach about 15,000 annually by 2018 (compared with 7,000 in 2001),
see IPPS RULE, page 20
see DOOMSDAY, Y page 16
Apps and other high-tech tools for promoting medication adherence.
Genotyping Test May Reduce Myopathy Risk
Contemporary Management of Hyponatremia See insert after page 18.
esearchers are using a new pharmacogenetic-based algorithm to predict patients who are abnormal metabolizers of statins and thus at risk for accumulating high blood levels of the drug, leading to debilitating, even fatal, cases of myopathy. “One of the common well-known side effects [of statins] is muscle aches, pains and weakness, which can occur in a large number of people—up
see GENOTYPING, page 8
From HOPA fall conference:
Launching Oncology IT System With Old + New Tech a Bad Idea
uccessfully implementing an electronic medical record (EMR) system requires, among other things, starting from scratch with a clean system, without importing databases from older systems in a misguided attempt to save time. That’s one of the lessons that Scott Soefje, PharmD, MBA, BCOP, the associate director of oncology pharmacy services at Smilow Cancer Hospital at Yale-New Haven Hospital (YNHH), in Connecticut, learned
Web Exclusive: Stakeholders debate merits of final sterile compounding bill. http://tinyurl.com/ppn-compounding
as YNHH went through the challenging process of implementing an EMR system that went live Feb. 1, 2013. Dr. Soefje was one of the team leaders during the implementation and also helped guide a second EMR rollout that went live last June at a sister hospital, the Hospital of Saint Raphael. (The hospitals have since combined into one location.) He shared some insights gleaned from both rollouts with
see NEW SYSTEM, page 29
New Product FDA Approves Enalapril for Children and Adults See page 33.
4 Up Front
Pharmacy Practice News • October 2013
CDC Calls for Antibiotic Stewardship In Report on Drug-Resistant Pathogens
The five most-viewed articles last month on pharmacypracticenews.com: 1. Tips for Surviving “The Unthinkable” in Patient Safety 2. Pharmacists Feeling Pain Over AMA Resolution 3. Are You Confident About Your Sterile Compounding QI Plan? 4. To Insource or Outsource? That Is the Question! 5. Getting Ready for Joint Commission Surveys Register for free at pharmacypracticenews.com to read these and other articles on the latest developments in hospital pharmacy.
‘We docs can’t run the show by ourselves. Medical care is a team sport. We are all taking care
of patients and can’t do it right if our egos get in the way.’ —“drmfr” See article, page 34
Via website Aug. 8, 2013
ntibiotic-resistant pathogens infect at least 2 million people in the United States each year, according to a report by the Centers for Disease Control and Prevention (CDC). Clostridium difficile, carbapenemresistant Enterobacteriaceae (CRE) and drug-resistant Neisseria gonorrhoeae received the highest hazard level, “urgent,” under the CDC’s new classification system. “For the first time ever, we’ve had a snapshot of antimicrobial resistance threats that have the most impact on human health,” said Tom Frieden, MD, MPH, director of the CDC, in a Sept. 16 media briefing. Of the 2 million annual infections, the CDC estimates that roughly 23,000 are fatal. The organization stressed that these numbers are conservative approximations based on hospital infections, and did not include data from nursing homes, dialysis facilities, long-term care hospitals or assisted living facilities. The CDC ranked 18 common drug-resistant pathogens using the following criteria: clinical and economic impact, current incidence, 10-year projected incidence, transmissibility, availability of effective antibiotics and barriers to prevention. Pathogens were categorized as urgent, serious or concerning hazard levels. Of the urgent threats, CRE, which is resistant to almost all antibiotics, causes 9,000 infections annually, and there are an estimated 246,000 new cases of drug-resistant gonorrhea each year. Although C. difficile does not yet show significant antibiotic resistance, it frequently infects patients treated with other antimicrobials and causes 250,000 hospitalizations annually. The CDC classified multidrug-resistant Acinetobacter, r drug-resistant Campylobacter, r fluconazole-resistant Candida, extended spectrum β-lactamaseproducing Enterobacteriaceae, vancomycin-resistant Enterococci, multidrug-resistant Pseudomonas aeruginosa, drug-resistant non-typhoidal Salmonella, drug-resistant Salmonella typhi, drug-resistant Shigella, methicillin-resistant Staphylococcus aureus, drug-resistant Streptococcus pneumoniae and drug-resistant tuberculosis as serious threats. The concerning threats were vancomycin-resistant Staphylococcus aureus, erythromycinresistant Group A Streptococcus and clindamycin-resistant Group B Streptococcus. “When we’re dealing with untreatable infections, we no longer have the second-tier drug to rely on,” said Michael Bell, MD, deputy director of CDC’s Division of Healthcare Quality Promotion. “That’s when it becomes a life-or-death matter.” The CDC used the report as a call to action for better stewardship of antibiotics. “Up to half of antibiotic use in humans in this country is either unnecessary or inappropriate,” Dr. Frieden said. “We have a lot of room for improvement.” Patients must understand there is a difference between more medication and the correct medication, he said. In addition to improving antibiotic prescription and use, the CDC report also recommended preventing infections through immunization, handwashing and safe food preparation. “If we don’t take action urgently, the medicine cabinet may be empty for patients with lifethreatening infections in coming months and years,” Dr. Frieden said. “But we do see a real ray of hope in the effective interventions that can prevent and reverse drug resistance.” —Ben Guarino
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Pharmacy Practice News • October 2013
WHO Recommends Earlier Treatment for HIV T
he World Health Organization (WHO) has released updated guidelines on the use of antiretroviral therapy (ART) for the treatment and prevention of HIV. The most significant change, according to HIV experts, is the WHO’s recommendation to start ART at the CD4 threshold of 500 cells/ mm3 or less in all adults, adolescents and older children. This update is part of what the authors called “a consistent global trend toward expanding access and the earlier initiation of treatment.” According to a press release from the Joint United Nations Programme on HIV/AIDS, about 25.9 million people will now be eligible for ART—9.2 million more than the 2010 guidelines that recommended treatment at a CD4 count of 350 cells/mm3 or less. Additionally, the WHO advises the initiation of ART regardless of CD4 cell count for certain populations, including pregnant and breastfeeding women, children younger than the age of 5 years, HIV-positive partners in serodiscordant couples and individuals coinfected with active tuberculosis disease or hepatitis B virus with severe chronic liver disease. The WHO does recognize resource limitations inherent to low- and middle-income countries. While calling for a CD4 threshold of 500 cells/mm3, the guidelines state, “Priority should be given to individuals with severe or advanced HIV disease and those with CD4 count of 350 cells/mm3 or less.” According to the guidelines, the firstline regimen for adults should consist of tenofovir disoproxil fumarate (TDF) plus lamivudine or emtricitabine (FTC) plus efavirenz (EFV), as a fixed-dose combination. Stavudine should not be used in first-line regimens due to metabolic toxicity. Treatment failure and efficacy should be assessed using viral load monitoring. The guidelines consolidate a range of WHO clinical recommendations and resources, making them available for the first time in a single document. Other new aspects include suggestions to decentralize HIV treatment and care by shifting tasks to properly trained health care workers. Philippa Easterbrook, MD, MPH, a senior scientist in the HIV Department at the WHO, in Geneva, noted that raising the CD4 thresholds for ART initiation to 500 cells, and recommending one preferred first-line regimen—one pill as a daily fixed-drug combination—were among the most important changes in the new guidelines. “The recommendation of one preferred regimen of a fixed-dose combination … will make it easier to prescribe, easier for adherence, and it will
also simplify drug procurement and the supply chain. The cost of this regimen (TDF/FTC/EFV) has also decreased in recent years,” said Dr. Easterbrook, who helped coordinate the overall development process for the guidelines. Paul Volberding, MD, director of the AIDS Research Initiative and director of research for Global Health Science at the University of California, San Francisco, agreed that the updated CD4 treatment threshold set by the WHO is a major improvement. But Dr. Volberding, who has helped develop guidelines for the International Antiviral Society–USA and the U.S. Department of Health and Human Services, pointed out that the WHO’s position is not a major break from existing treatment policy. “Both major guidelines in the United States recommend ART for everyone with HIV, regardless of CD4 cell count. This is functionally not different than the WHO guidelines because the vast majority of those infected with HIV have CD4 counts below 500 cells/ mm3. There is a growing convergence between the guidelines of the resourcerich and -limited countries,” he told Pharmacy Practice News. There are, however, some differences between the WHO guidelines and those released in the United States. “Because I work in a setting where resources aren’t constrained,” Dr. Volberding said, “I’m in
‘With their next guidelines revision, [the WHO will] recommend treating all [HIV-] infected people.’ —Paul Volberding,MD
favor of pregnant women continuing to be treated after the baby is born.” That position, he noted, is supported by U.S. treatment recommendations. The WHO guidelines, in contrast, “say a woman may have treatment discontinued after the baby is born and after breastfeeding is complete if she does not meet local treatment guidelines,” he pointed out. “I think the WHO will come around to changing that. With their next guidelines revision, they’ll likely recommend treating all infected people.” Implementing the new recommendations in resource-limited settings will present challenges, however. For example, how will funding be obtained for these new patients? “This is the question of the moment,” Dr. Volberding said. “Countries are talking about this now. How high up can they afford to go without running out of drugs and having to
stop treatment?” He urged more affluent countries not to be too critical of poorer nations that balk at the added expense. “The guidelines [are] at least aspirational. We’ll see a trend upward.” Despite economic and resource advantages found in the industrialized world, Dr. Easterbrook believes these regions also face HIV-related challenges. In such locales, “the challenge is that a significant proportion of HIVinfected persons are unaware of their infection. As a result, these persons only present for care and are diagnosed when they are clinically unwell with already advanced disease. There is a need for improved access to and uptake of HIV testing.” —George Ochoa Drs. Easterbrook and Volberding reported no relevant conﬂicts of interest.
WHO HIV Treatment Guidelines: A Pharmacist’s Perspective Jennifer Cocohoba, PharmD, BCPS, AAHIVP Health Sciences Associate Clinical Professor Department of Clinical Pharmacy UCSF School of Pharmacy Clinical Pharmacist UCSF Women’s HIV Program San Francisco, Calif.
June 2013 update brings the World Health Organization’s “Consolidated Guidelines on the Use of Antiretroviral Drugs for Treating and Preventing HIV Infection” into closer concordance with 2012 “Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents” issued by the U.S. Department of Health and Human Services, as well as the 2012 “Antiretroviral Treatment of Adult HIV Infection” recommendations of the International Antiviral Society-USA. These guidelines recommend antiretroviral therapy (ART) for all HIV-infected persons irrespective of CD4-positive cell count, acknowledging that the level of supportive evidence for this varies at different CD4-positive cell count thresholds. Accordingly, the WHO has expanded its recommendations to include treatment for all HIV-positive persons with CD4-positive cell counts less than 500 cells/mm3 (with priority to those with advanced disease or CD4-positive cell counts <350 cells/mm3), all HIV-positive pregnant women, all patients coinfected with hepatitis B or tuberculosis and all persons in serodiscordant relationships (i.e., where one partner is HIV-positive and the other is HIV-negative, which poses a question as to what level of sexual activity can occur, given the fact that practicing safer sex reduces but does not eliminate the risk for transmission to the HIV-negative partner). Although the WHO recommendations do
not yet recommend treatment for all HIV-infected patients, these changes represent a significant step forward in the challenge to scale up ART to make it accessible to all. The 2013 WHO guidelines endorse tenofovir/lamivudine/ efavirenz or tenofovir/emtricitabine/efavirenz, both available as a single-tablet regimen, as the preferred combinations for initial treatment of HIV. This is in line with many other HIV treatment guidelines that recommend therapies balancing efficacy, toxicity and simplicity. Interestingly, the WHO guidelines also recommend the efavirenz-containing combinations for HIV-positive pregnant women, irrespective of the trimester of pregnancy, and for women of childbearing age. U.S. HIV perinatal guidelines tend to be more conservative and avoid the use of efavirenz in women of childbearing age or women in their first trimester of pregnancy. WHO guidelines allow more latitude concerning continuation of ART postpartum, whereas other guidelines recommend that women remain on ART after childbirth. Practicing pharmacists can take a strong role in helping their countries meet the challenge of scaling up ART. The WHO guidelines offer recommendations for expanding HIV testing to community-based locations that can provide linkage to prevention, care and treatment. They recommend initiation of therapy in hospitals or peripheral health facilities but promote the maintenance of ART in community-based settings. They recommend newer technologies and techniques, such as cell phone–based interventions, to improve adherence. They also support task-shifting to trained nonphysician clinicians to initiate, maintain and dispense ART. Pharmacists working in community pharmacies or in other community-based settings have the potential to fulfill many of these WHO-outlined roles to support testing, treatment and care for HIV-infected patients worldwide.
Pharmacy Practice News • October 2013
New Guidelines Issued on Job-Related HIV Exposure T
he United States Public Health Service (USPHS) has released new guidelines on the management of occupational exposures to HIV and postexposure prophylaxis (PEP). Updated for the first time since 2005, the new guidelines include several important changes, most notably a recommendation that PEP regimens contain three or more antiretroviral drugs, as opposed to the two or three previously recommended, and that the regimen make use of newer, better tolerated medications. Raltegravir (Isentress, Merck), for example, an integrase inhibitor approved in 2007, has a better side-effect profile than the older drug zidovudine, which commonly causes nausea, vomiting, headache, insomnia and fatigue that can result in low adherence, the guidelines state. Due in part to its safer profile, raltegravir is now part of the preferred HIV PEP regimen, according to lead author David T. Kuhar, MD, a medical officer in
the Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention (CDC), in Atlanta. The preferred regimen also includes Gilead’s tenofovir (Viread) and emtricitabine (Emtriva), both of which were mentioned in the old guidelines, Dr. Kuhar noted. In addition to naming preferred agents, the updated guidelines also include important revisions regarding alternative HIV PEP regimens, Dr. Kuhar said. Janssen’s darunavir (Prezista), etravirine (Intelenc) and rilpivirine (Edurant), which were not available at the time of the previous guidelines, are now recommended. The new guidelines (Infect ( Control 2013;34:875-892) were a team effort, Dr. Kuhar added. They were developed by an interagency USPHS working group that included members from the CDC,
‘I think the changes that most of us would have liked have been included.’ —Cristina Gruta, PharmD
National Institutes of Health, FDA and the Health Resources and Services Administration, with contributions from an external expert panel.
Assessing Risk Is Part Of Intervention Plan Previously, the USPHS recommended assessing the level of risk associated with an individual exposure to determine whether two or three drugs should be used. Now, in the new guidelines, three or more drugs are recommended as PEP in all cases. “There are two main improvements from a clinician’s standpoint,” said Julia Garcia-Diaz, MD, MS, the program director of the Infectious Diseases Fellowship at Ochsner Medical Center, in New Orleans, who was not associated with developing the guidelines. “One is that, with the previous guidelines, we used to try to assess risk, meaning we would have to ask ourselves, do we use two drugs or do we use three drugs? The USPHS updates now have made it simpler and easier: You use three drugs or more. From our standpoint, this is a big help. The other improvement is the new recommendations in terms of the drugs that can be given to patients. The new regimen is much better tolerated and easier to take.” Jennifer Cocohoba, PharmD, a health sciences associate clinical professor at the University of California, San Francisco (UCSF) School of Pharmacy, said that in her view, the addition of raltegravir is one of the more noteworthy aspects of the updated guidelines. The drug likely was added not only because of its better side-effect profile, but also due to the lower risk for resistance that comes with any new agent, noted Dr. Cocohoba, who also is a pharmacist in the UCSF Women’s HIV Program. The 2013 guidelines also include a new recommendation regarding HIV testing of an exposed health care worker: Such testing can be completed in as little as four months after exposure if a fourth-generation combination HIV p24 antigen-HIV antibody test is used. Otherwise, six months of follow-up test-
ing is recommended to rule out HIV, according to the USPHS. Other aspects of the guidelines are continued from the previous edition. For example, PEP should be started as soon as possible, preferably within hours of exposure, and should continue for four weeks, and expert consultation is recommended.
PEPline Offers Help One place where medical providers can obtain expert consultation, whether they are concerned about a needle stick or a splash of bloody fluid, is the PEPline ( 448-4911), one of three consultation services run by the National HIV/AIDS Clinicians’ Consultation Center (NCCC). Cristina Gruta, PharmD, a pharmacist specialist at the NCCC who works on the PEPline, said, “We already knew that the CDC/USPHS was updating the occupational exposure guidelines to HIV because our project director, Dr. Ronald Goldschmidt, served as a member of the expert panel convened by the authors. We’ve been using the spirit of the guidelines even prior to publication, because our organization is part of the expert HIV treatment community.” Asked about compliance with PEPline recommendations, Dr. Gruta said that when health care providers call back, “it’s rare that I would hear of a situation where they disagreed with what we recommended. I think our recommendations are pretty well received.” She noted that in 2012, the PEPline received approximately 10,000 occupational exposure calls, about 95% of which involved actual exposures as opposed to general informational questions. Asked what she would change in the guidelines if she could, Dr. Garcia-Diaz said, “I don’t think I would change anything. I think the changes that most of us would have liked have been included.” —George Ochoa Drs. Cocohoba, Gruta, and Kuhar reported no relevant ﬁnancial conﬂicts of interest. Dr. Garcia-Diaz disclosed that she is on the speakers’ bureau for Pﬁzer.
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Pharmacy Practice News • October 2013
GENOTYPING continued from page 1
to 10% or 15% of the patients who take them,” senior author Richard B. Kim, MD, a professor of medicine at the University of Western Ontario, London, Canada, told Pharmacy Practice News. “Although the vast majority are able to take statins, a small subset of those patients can go on to have ... rhabdomyolysis that sometimes leads to kidney failure and, in very rare cases, death. So the question then comes down to [whether] there [is] a way
of predicting those who may experience these types of side effects.” In the study, the researchers prospectively recruited 299 outpatients taking atorvastatin or rosuvastatin (Circ Cardiovasc Genett 2013;6:400-408). Fortyfivefold interpatient variability in statin concentration was found among patients taking the same drug and dose. Nearly 90% of the explainable variability in rosuvastatin concentration could be accounted for by two reduced-function transporter polymorphisms, one in the uptake transporter gene SLCO1B1 and
the other in the efflux transporter gene ABCG2. Explainable variability in atorvastatin level was almost equally divided between two polymorphisms in SLCO1B1 and activity of cytochrome enzyme CYP450 3A4. From these findings, the investigators designed an algorithm that includes recommendations for maximum atorvastatin and rosuvastatin doses, based on the patient’s age and transporter genotype. The doses were predicted to result in plasma concentrations of statins that would be lower than the
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‘A Great Paper’ “I think it’s a great paper,” said Jasmine Talameh, PharmD, PhD, a postdoctoral researcher at Ohio State University, in Columbus, who was not associated with the study. “There’s a lot of data in the literature on genetic variants associated with statin-induced myopathy. But a model combining those genetic variants for predicting statininduced myopathy hasn’t been established yet. This paper takes a step forward in doing that.” Asked whether the algorithm is ready to be used clinically, Dr. Kim said, “We do think the information provided in our published research can be [applied to patients]. What our algorithm does is serve as a statin selection and dosing decision-support tool for clinicians.” Dr. Talameh countered that “more research is needed. Concentration predictions need to be validated prospectively in an independent patient population. The gold standard after that would be prospectively validating the algorithm for association with not just concentration, but the clinical outcome of statin-induced myopathy.” Clinical use of the algorithm requires genotyping of the patient, which Dr. Kim said would cost $100 to $300. In the future, he noted, as a result of advances in the development of next-generation sequencing technology, “statin genotyping will be included as a part of a [large diagnostic] panel that could be done at once. So you basically buy the whole encyclopedia, and this [statins] would be just a chapter.” Insurers might pay for genotyping, but only “if there is increasing evidence that this is cost-effective.” Limitations of the study include a focus on only two of several commonly used statins and a predominantly white patient population, Dr. Kim noted. He added that he would like to see “a larger multicenter trial using our predictive algorithm versus standard care,” as well as research exploring the prevention of adverse reactions and severe muscle injury, overall health care costs, and noninferior or better cardiovascular outcomes and cholesterol lowering. —George Ochoa
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90th percentile, a value that reflects the fact that 10% of patients taking statins have statin-related muscle complaints. The researchers also retrospectively genotyped 579 patients from primary and specialty care databases in Canada and the United States. Genotypes associated with statin concentration were not differently distributed by statin dose, suggesting that clinicians had not optimized each patient’s statin serum level and that use of the algorithm thus might be beneficial.
Drs. Kim and Talameh reported no relevant ﬁnancial conﬂicts of interest.
Pharmacy Practice News • October 2013
Malnutrition Often Overlooked in Cancer Patients Washington—When it comes to providing enteral or parenteral nutrition to patients with cancer, the evidence shows the sooner an intervention is implemented, the better the outcomes. However, according to experts, malnutrition remains all too common. “A significant number of cancer patients have already experienced weight loss by the time they are diagnosed,” said Noreen Luszcz, RD, MBA, CNSC, the national home nutrition support program director at Walgreens Infusion Services in Deerfield, Ill.
fied as being at risk for malnutrition, the nurse and a dietitian make recommendations to the treating physician to improve the patient’s nutritional status. “The clinician may provide guidance to the patient as to how to increase calories and protein, as well as recommending use of oral supplements,” she said. “If the patient continues to deteriorate nutritionally, enteral [EN]
or parenteral nutrition [PN] may be indicated.”
Screening Tools Available Nutritional assessment tools such as the Patient-Generated Subjective Global Assessment and the Malnutrition Screening Tool are widely available to clinicians, so it is not the absence of screening tools that accounts for untimely malnutrition screening and intervention.
Furthermore, Ms. Luszcz said clinicians who find these tools too cumbersome can simply use observed weight changes to decide on the necessity for a nutritional intervention and how aggressive it should be (Table).
Barriers to Best Practice One way to improve detection and intervention could be to educate
see MALNUTRITION, page 10
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‘A significant number of cancer patients have already experienced weight loss by the time they are diagnosed.’
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—Noreen Luszcz, RD, MBA, CNSC
Table. Changes in Body Weight as Nutritional Intervention Triggers
Significant Weight Loss, %
Severe Weight Loss, %
Source: Luszcz N, ONS abstract 363, adapted from Blackburn GL et al. J Parenter Enteral Nutr. 1977;1:11-22.
In a poster she presented at the Oncology Nursing Society’s 38th Annual Congress (abstract 363), Ms. Luszcz noted that the American Society of Parenteral and Enteral Nutrition recommends screening cancer patients for nutritional status frequently and intervening early if necessary (JPEN ( 2009;33:472-500). Nutritional support is more beneficial to patients when they are undernourished, with only minor weight loss, than when they are severely malnourished after significant weight loss, she said (Clin Nutr 2009;28:445-454). “Every new patient admitted to Walgreens home infusion services ... undergoes a complete nutrition evaluation, which includes a review of the patient’s diet, appetite, [and] weight and a comprehensive gastrointestinal system review,” she told Pharmacy Practice News. If a patient is identi-
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Pharmacy Practice News • October 2013
Quality Cancer Care: No Longer Just About Survival Washington—The definition of quality is shifting in today’s rapidly changing field of cancer care, and clinicians need to step it up when explaining treatment options to patients and helping them achieve their goals, a panel told community oncologists at the Association of Community Cancer Centers’ national meeting. Oncology used to have one measure of quality—survival, said moderator Cliff Goodman, PhD, a senior vice president and principal of The Lewin Group, a health care consulting firm. Now survival is only one of many things physicians are asked to measure. There are a few trends forcing a change in how quality is assessed. “Imperatives to spend wisely have really changed our definitions of quality to one of value,” said Randall Oyer, MD, the medical director of the cancer program at Lancaster General Hospital, in Pennsylvania. Additionally, today’s patients are more engaged and empowered, and have different expectations. Finally, the complexity of care requires the development of new methods of communication. Baby boomers are now 67 years old, the median age of cancer diagnosis, said Linda House, RN, BSN, the executive vice president of external affairs for the Cancer Support Community
At a Glance Three important factors affecting how oncologists’ care is judged: • The value of therapies, as opposed to solely survival • Patients’ increasing knowledge of practice standards and new research • Complexity of new treatment options demanding better communication
MALNUTRITION continued from page 9
clinicians on the benefits of adequate nutrition, including the lower mortality risk associated with the intervention ((J Parenter Enteral Nutr 2007;31:451455), according to Randy Fasnacht, RPh, the director of pharmacy at Advanced Infusion Services in Akron,
of Washington, D.C., a nonprofit organization providing support and education to people affected by cancer. Seventy-seven percent of cancers are diagnosed in people aged 55 and older, she said: “We’re seeing this swoon of very empowered people who either are or have been making health care decisions on the part of their parents and are now doing so for themselves. We have a real opportunity to engage these decision makers in a different way than we have in previous generations.” John Fox, MD, the associate vice president of medical affairs for Priority Health, a health plan in Michigan, said there are many measurable factors that affect patient outcomes. “There’s a tremendous amount of information on patients’ understanding of their cancer condition that impacts decisions, including end-of-life treatment,” he said. Despite these clear changes, defining quality isn’t easy in a field like oncology, which has many variables. “We’ve been accustomed for a long time to thinking about cancer as an acute illness, and now it’s chronic disease management, which none of us in oncology training really expected to happen,” Dr. Oyer said. Data management of quality measures also is critical, Dr. Fox said. And physicians and payors working in partnership need to make sure the right things are being rewarded. “If we want discussions around endof-life care and patient goals and priorities to occur, we have to recognize that’s an important determinant of outcome, and we should pay for that,” he said. “We have to recognize that it takes time not only to plan a chemo regimen but equally important, you have a conversation that educates a patient on that regimen and whether or not it’s curative.” Ms. House said she worries that physicians aren’t always transparent in the reasons why they make certain decisions within clinical pathways. More than half of the 3,600 patients in her organization’s patient experience registry reported a treatment decision being made during their first oncologist visit,
yet only 15% said they received information to support the choice. But pathways, on balance, are positive and help physicians know what choices are reasonable, according to Dr. Oyer. “I don’t think using pathways necessarily takes out the customization for patient preferences, or social/cultural background. In any industry, standardization improves safety and efficiency,” he said. Pathways were never meant to demand 100% compliance, Dr. Fox said. In his organization, individual oncology practices can determine their preferred regimens, but if they have a patient who needs to vary from that regimen for good reason, “that’s fine with us.” Panelists agreed that currently, the idea of including the patient voice as part of quality conversations is mostly lip service. “We still fall down on what defines quality and value from the patient perspective in oncology,” Ms. House said. Providers should do distress screening as part of a pathway, within so many days of cancer diagnosis or making a health care decision, she said. The main causes of patient distress are fatigue, sexual dysfunction, sleep issues, weight loss and worry about the future, she said: “These are things we don’t measure in traditional ways.” Payors are willing to pay for services
that support the “triple aim” of patient experience, health outcomes and total cost of care, Dr. Fox said, “but we have to find things that balance all three of those.” Ms. House said her organization has tools patients can use to have conversations with their health care teams about how pathway decisions are made, what the incentives are, how much it will cost patients and their insurance carriers, and what incentives favor one plan versus another. Patients know what they want as long as they’re asked, Dr. Fox said. “We don’t have the infrastructure in place to make sure we engage patients in those discussions and hear what’s most important to them, like being able to travel or spend time with family,” he said. Evidence suggests that patients get more care than they want, had they known what the options were, he said. Often, patients get treatments because they think that’s what their families want, and families want patients to get treatments because they think that’s what the patient wants. “The overall measure of quality from my frame of reference,” he said, “is that we’re providing the care that the patients wanted.” —Karen Blum
Ohio. “There are still those physicians who believe that if you feed the patient, you feed the tumor,” said Mr. Fasnacht, who was not involved in the abstract. Mr. Fasnacht added that even clinicians who know about the risks for malnutrition and use screening tools face administrative barriers to timely intervention. “Insurance companies and Medicare and Medicaid
are the thorn in everybody’s side,” he said. “You need to make sure you have reams and reams of documentation showing EN or PN are justified if you want to go ahead with it.” The need to overcome these educational and administrative barriers, as well as any others that prevent timely screening and nutritional intervention, is imperative, noted Mr. Fasnacht. “The
fact is we need to think about ensuring adequate nutrition from day one.”
Evolving treatments demand better communication from oncologists.
—David Wild Ms. Luszcz and Mr. Fasnacht reported no relevant ﬁnancial conﬂicts of interest. Mr. Fasnacht requested that his colleague, Talon Schroyer, a 2014 PharmD candidate, be cited as a contributor to the research that informed Mr. Fasnacht’s comments.
Pharmacy Practice News • October 2013
Hem/Onc Pharmacy Virtual cancer centers:
A Panacea for the Rising Costs of Coordinated Care? Washington—In an era when W patients, providers and insurers are demanding increased coordination of cancer care services but the costs of establishing freestandingg cancer centers run in the multimiillion-dollar range, hospitals and health lth systems should consider forming “virtual” cancer centers as less capitalintensive alternatives, said presenters at the Association of Community Cancer Centers’ national meeting. For health systems spread out over multiple campuses or cities, “it may be physically impossible, or unrealistic, to centralize or consolidate all cancer care services,” said Matt Sturm, MBA, a senior manager with ECG Management Consultants’ office in Seattle. But, thinking outside the box, such systems can work to establish a virtual cancer center, in which services normally offered by a single cancer center are organized so that patients and providers can easily access them throughout the system, Mr. Sturm said.
Hawaii Pacific Goes Virtual A virtual center has been working well for Hawaii Pacific Health (HPH), a network of four hospitals and 44 outpatient clinics across six Hawaiian islands, said Kristen Chun, RN, MBA, the executive director of HPH’s oncology service line, in Honolulu. HPH offers adult oncology, pediatric oncology and women’s oncology, and, through partnerships with additional health providers, radiation oncology and clinical trials. Most services are based on Oahu, yet there is also a need to provide services to patients living on the neighboring islands. “It’s really important that our network reach out statewide,” Ms. Chun said. “It’s not uncommon to have patients on Kauai be diagnosed with a serious form of cancer that requires radiation therapy and simply opt out of treatment because they have no interest in traveling to Oahu for six-week periods of time. “What we’re interested in doing is letting patients know we have all the components of a one-site building, but we share them in the community and provide care where the patient is. That’s the model that is going to be the most successful for us.” Some patients do travel to other islands for care, and the local Blue Cross and Blue Shield will occasionally fly patients to the mainland United States for treatments not offered locally, such as bone marrow transplant. In 2010, HPH worked with Mr. Sturm’s group to evaluate what they could do to better serve patients. Reviews showed
A virtual approach to coordinated care helps sidestep the financial burden of building a single comprehensive cancer center. that although the individual clinical programs were very good, leaders needed to improve leveraging of programs across the system. Patients and some referring physicians were “very clueless” about the services offered by HPH, Ms. Chun said: “They would see one hospital, and one site of service, and think that’s what we had, not understanding that the four hospitals can provide pretty much any service you need.” Executives also discovered there were some redundancies in programs, there was no overriding physician leadership, and each hospital was focused on its own needs without an overarching direction. Over the past two and a half years, HPH executives have worked to improve organizational structure, operations, technology and marketing. They named a medical director and an executive director of oncology, who work with the hospital chief operating officers (COOs) and report to HPH leadership. These leaders work with the hospitals’ COOs, chief medical officers and oncology program
m managers to review program needs and share resources. All hospitals and clinics use the Epic electronic medical records (EMR) system, which allows for a seamless experience for patients and offers leaders easy access to volumes and outcomes data. They’re working to implement Epic in community physician offices; 150 joined them last year. They also are developing a comprehensive marketing tool to emphasize the scope and quality of services, Ms. Chun said. “We have the second largest market share in the state, so we’re not out there necessarily to battle for market share. We are out there to make sure that when our patients come to us, we provide them with quality, coordinated care,” she added. Organizations looking to establish virtual cancer centers first need a strategic plan outlining the intended geographic locations the center would serve, the scope of services to be provided, any need to increase alignment with oncologists, and how to improve focus on patients, Mr. Sturm said. Successful cancer programs have eight key elements, he said, the first three of which are crucial to a virtual cancer center: physician leadership and expertise; coordinated clinical care through efforts like patient navigation or tumor boards; consistent protocols based on National Comprehensive Cancer Network or other guidelines; investment in diagnostic and treatment technologies; patient support services; making clinical research available to patients; use of quality improvement tools; and screening, outreach and prevention services. Patient navigation, technology and
multidisciplinary care are the essential elements of clinical coordination in an oncology program, Mr. Sturm said. In virtual cancer programs, nurse navigators or trained lay personnel are critical to helping patients access clinical care and support services, and overcome logistical or financial barriers to care. The number and type of navigators should match the needs of the program. “Everyone in the program should know what services are offered throughout the organization, where to find those [services] and how to access them,” he said. A six- to eight-member leadership council of physicians and administrators with expertise from different tumor sites or specialties most often governs the centers. Each participating campus or location should be represented. Leaders need to provide strategic direction in research, technology, program development and quality. It is recommended that organizations have both an administrative and a physician leader, who dedicate time to the virtual center. EMRs also are key to keeping all providers up to date on patient care, and reducing the burden on patients of having to transport files from site to site. And, providers should work to offer multidisciplinary care, either through regular tumor conference meetings or teleconferences to review patient cases and devise treatment plans, or through multidisciplinary clinics where multiple specialists can see a patient in one visit. Finally, Mr. Sturm said, providers must develop and follow consistent clinical protocols so the same high-quality care is offered throughout the network. —Karen Blum
The Pharmacy Piece of the Virtual Puzzle
hen establishing any virtual health system, one has to consider pharmacy operations as an integral part of the clinical services mix. Pharmacists were part of a team working for two years to establish the Levine Cancer Institute, which opened last September as part of Carolinas HealthCare System. The system has more than 30 hospitals throughout North and South Carolina. Cancer patients are seen at 12 of those locations, including the main campus in Charlotte, N.C. The cancer institute aims to provide consistent high-quality patient care at all of its locations, according to Dragos Plesca, PharmD, PhD, a hematology/oncology clinical pharmacy specialist with the institute. “Communication and sharing of information is the most critical aspect,” Dr. Plesca said. “Being in contact with the other regional sites and providing them with all of the information necessary to establish the same practice as the main campus [is crucial].” To help streamline pharmacy operations, Dr. Plesca and colleagues developed standardized medication order sets that met the institute’s clinical pathway guidelines for all
malignancies, so that patients receive the same therapy whether at the main campus or a regional site. Because some locations differ in their mix of pharmacists and pharmacy technicians, the pharmacy team provides clear instructions for chemotherapy preparation to each site. The team also helps conduct site visits to ensure all protocols and procedures are followed. The pharmacy team also is exploring remote order verification and providing some of the satellite locations with pre-mixed chemotherapy and other agents. Meanwhile, pharmacists also worked to ensure consistent patient education. Andrea Bryant, PharmD, a clinical pharmacist with the cancer institute, helped develop information packets for each medication, including an explanation of what the drug is, its class, how it works, what to tell a physician before taking it, medication instructions, and information on proper storage and adverse side effects. Once an oncologist selects a medication regimen, all information automatically prints out for the patient. —K.B.
Indications and Usage NEXTERONE (amiodarone HCl) Premixed Injection is indicated for initiation of treatment and prophylaxis of frequently recurring ventricular ﬁbrillation (VF) and hemodynamically unstable ventricular tachycardia (VT) in patients refractory to other therapy. NEXTERONE also can be used to treat patients with VT/VF for whom oral amiodarone is indicated, but who are unable to take oral medication. During or after treatment with NEXTERONE, patients may be transferred to oral amiodarone therapy. Use NEXTERONE for acute treatment until the patient’s ventricular arrhythmias are stabilized. Most patients will require this therapy for 48 to 96 hours, but NEXTERONE may be safely administered for longer periods if necessary.
Important Risk Information NEXTERONE (amiodarone HCl) Premixed Injection is contraindicated in patients with: • Known hypersensitivity to any of the components of NEXTERONE, including iodine • Cardiogenic shock • Marked sinus bradycardia • Second- or third-degree atrio-ventricular (AV) block unless a functioning pacemaker is available • NEXTERONE should be administered only by physicians who are experienced in the treatment of life-threatening arrhythmias, who are thoroughly familiar with the risks and beneﬁts ﬁ of amiodarone therapy, and who have access to facilities adequate for monitoring the effectiveness and side effects of treatment. • Hypotension is the most common adverse reaction seen with intravenous amiodarone. In clinical trials, treatment-emergent, drug-related hypotension was reported in 16% (288/1836) of patients treated with intravenous amiodarone. Clinically signiﬁcant ﬁ hypotension during infusions was seen most often in the ﬁrst several hours of treatment and appeared to be related to the rate of infusion. Monitor the initial rate of infusion closely and do not exceed the recommended rate. In some cases, hypotension may be refractory and result in a fatal outcome. Treat hypotension initially by slowing the infusion; additional standard therapy may be needed, including: vasopressors, positive inotropic agents and volume expansion. • In 4.9% (90/1836) of patients in clinical trials, drug-related bradycardia that was not dose-related occurred while patients were receiving intravenous amiodarone for life-threatening VT/VF. Treat bradycardia by slowing the infusion rate or discontinuing NEXTERONE. Treat patients with a known predisposition to bradycardia or AV block with NEXTERONE in a setting where a temporary pacemaker is available. • Elevations of blood hepatic enzyme values ALT, AST, GGT are commonly seen in patients with immediately life-threatening VT/VF. / In patients with life-threatening arrhythmias, the potential risk of hepatic injury should be weighed against the potential beneﬁt of NEXTERONE therapy. Carefully monitor patients receiving NEXTERONE for evidence of progressive hepatic injury. In such cases, consider reducing the rate of administration or withdrawing NEXTERONE. • Like all antiarrhythmics, NEXTERONE may cause worsening of existing arrhythmias or precipitate a new arrhythmia. Monitor patients for QTc prolongation during infusion with NEXTERONE. Reserve the combination of amiodarone with other antiarrhythmic therapies that prolong the QTc to patients with life-threatening ventricular arrhythmias who are incompletely responsive to a single agent. • There have been postmarketing reports of acute-onset (days to weeks) pulmonary injury in patients treated with intravenous amiodarone. Findings included pulmonary inﬁ ﬁltrates and masses on X-ray, bronchospasm, wheezing, fever, dyspnea, cough, hemoptysis, and hypoxia. Some cases have progressed to respiratory failure or death. Two percent (2%) of patients were reported to have acute respiratory distress syndrome (ARDS) during clinical studies involving 48 hours of therapy. Pulmonary toxicity including pulmonary ﬁﬁbrosis is a well-recognized complication of long-term amiodarone use. • Amiodarone inhibits peripheral conversion of thyroxine (T4) to triiodothyronine (T3) and may cause increased T4 levels, decreased T3 levels, and increased levels of inactive reverse T3 (rT3) in clinically euthyroid patients. Amiodarone can cause either hypothyroidism or hyperthyroidism. Evaluate thyroid function prior to treatment and periodically thereafter, particularly in elderly patients, and in any patient with a history of thyroid nodules, goiter, or other thyroid dysfunction. Because of the slow elimination of amiodarone and its metabolites, high plasma iodide levels, altered thyroid function, and abnormal thyroid function tests may persist for several weeks or even months following NEXTERONE withdrawal. • The most important adverse reactions were hypotension, asystole/cardiac arrest/pulseless electrical activity (PEA), cardiogenic shock, congestive heart failure, bradycardia, liver function test abnormalities, VT, and AV block. The most common adverse reactions leading to discontinuation of intravenous amiodarone therapy were hypotension (1.6%), asystole/cardiac arrest/PEA (1.2%), VT (1.1%), and cardiogenic shock (1%). • Drug Interactions • Since amiodarone is a substrate for CYP3A and CYP2C8, drugs/substances that inhibit these isoenzymes may decrease the metabolism and increase serum concentration of amiodarone. • Amiodarone inhibits p-glycoprotein and certain CYP450 enzymes, including CYP1A2, CYP2C9, CYP2D6, and CYP3A. This inhibition can result in unexpectedly high plasma levels of other drugs which are metabolized by those CYP450 enzymes or are substrates for p-glycoprotein. HMG-CoA reductase inhibitors that are CYP3A4 substrates in combination with amiodarone have been associated with reports of myopathy/rhabdomyolysis. Limit the dose of simvastatin in patients on amiodarone to 20 mg daily. Limit the daily dose of lovastatin to 40 mg. Lower starting and maintenance doses of other CYP3A4 substrates (e.g., atorvastatin) may be required. • Some drugs/substances are known to accelerate the metabolism of amiodarone by stimulating the synthesis of CYP3A (enzyme induction). This may lead to low amiodarone serum levels and potential decrease in efﬁ ﬁcacy. Fluoroquinolones, macrolide antibiotics, and azoles are known to cause QTc prolongation. There have been reports of QTc prolongation, with or without TdP, in patients taking amiodarone when ﬂuoroquinolones, macrolide antibiotics, or azoles were administered concomitantly. Please see brief summary of Full Prescribing Information on the following pages.
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NEXTERONE (amiodarone HCl) Premixed Injection for intravenous use Brief Summary of Prescribing Information. See PI for Full Prescribing Information. 1 INDICATIONS AND USAGE NEXTERONE is indicated for initiation of treatment and prophylaxis of frequently recurring ventricular ﬁbrillation (VF) and hemodynamically unstable ventricular tachycardia (VT) in patients refractory to other therapy. NEXTERONE also can be used to treat patients with VT/VF for whom oral amiodarone is indicated, but who are unable to take oral medication. During or after treatment with NEXTERONE, patients may be transferred to oral amiodarone therapy [see Dosage and Administration (2) in full prescribing information]. Use NEXTERONE for acute treatment until the patient’s ventricular arrhythmias are stabilized. Most patients will require this therapy for 48 to 96 hours, but NEXTERONE may be safely administered for longer periods if necessary. 4 CONTRAINDICATIONS NEXTERONE is contraindicated in patients with: • Known hypersensitivity to any of the components of NEXTERONE Premixed Injection, including iodine. Hypersensitivity reactions may involve rash, angioedema, cutaneous/mucosal hemorrhage (bleeding), fever, arthralgias (joint pains), eosinophilia (abnormal blood counts), urticaria (hives), thrombotic thrombocytopenic purpura, or severe periarteritis (inﬂammation around blood vessels). • Cardiogenic shock. • Marked sinus bradycardia. • Second- or third-degree atrio-ventricular (AV) block unless a functioning pacemaker is available. 5 WARNINGS AND PRECAUTIONS NEXTERONE should be administered only by physicians who are experienced in the treatment of life-threatening arrhythmias, who are thoroughly familiar with the risks and beneﬁts of amiodarone therapy, and who have access to facilities adequate for monitoring the effectiveness and side effects of treatment. 5.1 Hypotension Hypotension is the most common adverse reaction seen with intravenous amiodarone. In clinical trials, treatment-emergent, drug-related hypotension was reported as an adverse effect in 288 (16%) of 1836 patients treated with intravenous amiodarone. Clinically signiﬁcant hypotension during infusions was seen most often in the ﬁrst several hours of treatment and was not dose related, but appeared to be related to the rate of infusion. Hypotension necessitating alterations in intravenous amiodarone therapy was reported in 3% of patients, with permanent discontinuation required in less than 2% of patients. Treat hypotension initially by slowing the infusion; additional standard therapy may be needed, including the following: vasopressor drugs, positive inotropic agents, and volume expansion. Monitor the initial rate of infusion closely and do not exceed the recommended rate [see Dosage and Administration (2) in full prescribing information]. In some cases, hypotension may be refractory and result in a fatal outcome [see Adverse Reactions (6.2) in full prescribing information]. 5.2 Bradycardia and Atrio-ventricular Block In 90 (4.9%) of 1836 patients in clinical trials, drug-related bradycardia that was not dose-related occurred while they were receiving intravenous amiodarone for life-threatening VT/VF. Treat bradycardia by slowing the infusion rate or discontinuing NEXTERONE. In some patients, inserting a pacemaker is required. Despite such measures, bradycardia was progressive and terminal in 1 patient during the controlled trials. Treat patients with a known predisposition to bradycardia or AV block with NEXTERONE in a setting where a temporary pacemaker is available. 5.3 Liver Enzyme Elevations Elevations of blood hepatic enzyme values [alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT)] are commonly seen in patients with immediately life-threatening VT/VF. Interpreting elevated AST activity can be difﬁcult because the values may be elevated in patients who have had recent myocardial infarction, congestive heart failure, or multiple electrical deﬁbrillations. Approximately 54% of patients receiving intravenous amiodarone in clinical studies had baseline liver enzyme elevations, and 13% had clinically signiﬁcant elevations. In 81% of patients with both baseline and on-therapy data available, the liver enzyme elevations either improved during therapy or remained at baseline levels. Baseline abnormalities in hepatic enzymes are not a contraindication to treatment. Acute, centrolobular conﬂuent hepatocellular necrosis leading to hepatic coma, acute renal failure, and death has been associated with the administration of intravenous amiodarone at a much higher loading dose concentration and much faster rate of infusion than recommended [see Dosage and Administration (2) in full prescribing information]. In patients with life-threatening arrhythmias, the potential risk of hepatic injury should be weighed against the potential beneﬁt of NEXTERONE therapy. Carefully monitor patients receiving NEXTERONE for evidence of progressive hepatic injury. In such cases, consider reducing the rate of administration or withdrawing NEXTERONE. 5.4 Proarrhythmia Like all antiarrhythmic agents, NEXTERONE may cause a worsening of existing arrhythmias or precipitate a new arrhythmia. Proarrhythmia, primarily torsade de pointes (TdP), has been associated with prolongation, by intravenous amiodarone, of the QTc interval to 500 ms or greater. Although QTc prolongation occurred frequently in patients receiving intravenous amiodarone, TdP or new-onset VF occurred infrequently (less than 2%). Monitor patients for QTc prolongation during infusion with NEXTERONE. Reserve the combination of amiodarone with other antiarrhythmic therapies that prolong the QTc to patients with life-threatening ventricular arrhythmias who are incompletely responsive to a single agent. Fluoroquinolones, macrolide antibiotics, and azoles are known to cause QTc prolongation. There have been reports of QTc prolongation, with or without TdP , in patients taking amiodarone when ﬂuoroquinolones, macrolide antibiotics, or azoles were administered concomitantly [see Drug Interactions (7) in full prescribing information].
Amiodarone causes thyroid dysfunction in some patients, which may lead to potentially fatal breakthrough or exacerbated arrhythmias. 5.5 Pulmonary Disorders Early-onset Pulmonary Toxicity There have been postmarketing reports of acute-onset (days to weeks) pulmonary injury in patients treated with intravenous amiodarone. Findings have included pulmonary inﬁltrates and masses on X-ray, bronchospasm, wheezing, fever, dyspnea, cough, hemoptysis, and hypoxia. Some cases have progressed to respiratory failure or death. ARDS Two percent (2%) of patients were reported to have adult respiratory distress syndrome (ARDS) during clinical studies involving 48 hours of therapy. Pulmonary Fibrosis Only 1 of more than 1000 patients treated with intravenous amiodarone in clinical studies developed pulmonary ﬁbrosis. In that patient, the condition was diagnosed 3 months after treatment with intravenous amiodarone, during which time the patient received oral amiodarone. Pulmonary toxicity is a well-recognized complication of long-term amiodarone use (see package insert for oral amiodarone). 5.6 Loss of Vision Cases of optic neuropathy and optic neuritis, usually resulting in visual impairment, have been reported in patients treated with oral amiodarone. In some cases, visual impairment has progressed to permanent blindness. Optic neuropathy and neuritis may occur at any time following initiation of therapy. A causal relationship to the drug has not been clearly established. Perform an ophthalmic examination if symptoms of visual impairment appear, such as changes in visual acuity and decreases in peripheral vision. Re-evaluate the necessity of amiodarone therapy if optic neuropathy or neuritis is suspected. Perform regular ophthalmic examination, including fundoscopy and slit-lamp examination, during administration of NEXTERONE. 5.7 Long-Term Use There has been limited experience in patients receiving intravenous amiodarone for longer than 3 weeks. See package insert for oral amiodarone. 5.8 Thyroid Abnormalities Amiodarone inhibits peripheral conversion of thyroxine (T4) to triiodothyronine (T3) and may cause increased T4 levels, decreased T3 levels, and increased levels of inactive reverse T3 (rT3) in clinically euthyroid patients. Amiodarone is also a potential source of large amounts of inorganic iodine and can cause either hypothyroidism or hyperthyroidism. Evaluate thyroid function prior to treatment and periodically thereafter, particularly in elderly patients, and in any patient with a history of thyroid nodules, goiter, or other thyroid dysfunction. Because of the slow elimination of amiodarone and its metabolites, high plasma iodide levels, altered thyroid function, and abnormal thyroid function tests may persist for several weeks or even months following NEXTERONE withdrawal. There have been postmarketing reports of thyroid nodules/thyroid cancer in patients treated with amiodarone. In some instances hyperthyroidism was also present [see Adverse Reactions (6.2) in full prescribing information]. Hyperthyroidism and Thyrotoxicosis Hyperthyroidism occurs in about 2% of patients receiving amiodarone, but the incidence may be higher among patients with prior inadequate dietary iodine intake. Amiodarone-induced hyperthyroidism usually poses a greater hazard to the patient than hypothyroidism because of the possibility of thyrotoxicosis and arrhythmia breakthrough or aggravation, all of which may result in death. There have been reports of death associated with amiodarone-induced thyrotoxicosis. Consider the possibility of hyperthyroidism if any new signs of arrhythmia appear. Identify hyperthyroidism by relevant clinical signs and symptoms, subnormal serum levels of thyroid stimulating hormone (TSH), abnormally elevated serum free T4, and elevated or normal serum T3. Since arrhythmia breakthroughs may accompany amiodarone-induced hyperthyroidism, aggressive medical treatment is indicated, including, if possible, dose reduction or withdrawal of amiodarone. Amiodarone hyperthyroidism may be followed by a transient period of hypothyroidism. The institution of antithyroid drugs, Ƶ-adrenergic blockers or temporary corticosteroid therapy may be necessary. The action of antithyroid drugs may be especially delayed in amiodarone-induced thyrotoxicosis because of substantial quantities of preformed thyroid hormones stored in the gland. Radioactive iodine therapy is contraindicated because of the low radioiodine uptake associated with amiodarone-induced hyperthyroidism. When aggressive treatment of amiodarone-induced thyrotoxicosis has failed or amiodarone cannot be discontinued because it is the only drug effective against the resistant arrhythmia, surgical management may be an option. Experience with thyroidectomy as a treatment for amiodarone-induced thyrotoxicosis is limited, and this form of therapy could induce thyroid storm. Therefore, surgical and anesthetic management require careful planning. Neonatal Hypo- or Hyperthyroidism Amiodarone can cause fetal harm when administered to a pregnant woman. Although amiodarone use during pregnancy is uncommon, there have been a small number of published reports of congenital goiter/hypothyroidism and hyperthyroidism associated with oral administration. Inform the patient of the potential hazard to the fetus if NEXTERONE is administered during pregnancy or if the patient becomes pregnant while taking NEXTERONE. Hypothyroidism Hypothyroidism has been reported in 2% to 4% of patients in most series, but in 8% to 10% in some series. This condition may be identiﬁed by relevant clinical symptoms and particularly by elevated serum TSH levels. In some clinically hypothyroid amiodarone-treated patients, free thyroxine index values may be normal. Manage hypothyroidism by reducing the NEXTERONE dose and considering the need for thyroid hormone supplement. However, therapy must be individualized, and it may be necessary to discontinue oral amiodarone in some patients.
5.9 Surgery Perform close perioperative monitoring in patients undergoing general anesthesia who are on amiodarone therapy as they may be more sensitive to the myocardial depressant and conduction defects of halogenated inhalational anesthetics.
Nervous System: hallucination, confusional state, disorientation, and delirium, pseudotumor cerebri
5.10 Corneal Refractive Laser Surgery Advise patients that most manufacturers of corneal refractive laser surgery devices contraindicate corneal refractive laser surgery in patients taking amiodarone.
Respiratory: y bronchospasm, possibly fatal respiratory disorders (including distress, failure, arrest and ARDS), bronchiolitis obliterans organizing pneumonia (possibly fatal), dyspnea, cough, hemoptysis, wheezing, hypoxia, pulmonary inﬁltrates and /or mass, pleuritis
5.11 Electrolyte Disturbances Correct hypokalemia or hypomagnesemia whenever possible before initiating treatment with NEXTERONE, as these disorders can exaggerate the degree of QTc prolongation and increase the potential for TdP. Give special attention to electrolyte and acid-base balance in patients experiencing severe or prolonged diarrhea or in patients receiving concomitant diuretics.
Thyroid: d thyroid nodules/thyroid cancer
6 ADVERSE REACTIONS 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reﬂect the rates observed in practice. In a total of 1836 patients in controlled and uncontrolled clinical trials, 14% of patients received intravenous amiodarone for at least one week, 5% received it for at least 2 weeks, 2% received it for at least 3 weeks, and 1% received it for more than 3 weeks, without an increased incidence of severe adverse reactions. The mean duration of therapy in these studies was 5.6 days; median exposure was 3.7 days. The most important adverse reactions were hypotension, asystole/cardiac arrest/pulseless electrical activity (PEA), cardiogenic shock, congestive heart failure, bradycardia, liver function test abnormalities, VT, and AV block. Overall, treatment was discontinued for about 9% of the patients because of adverse reactions. The most common adverse reactions leading to discontinuation of intravenous amiodarone therapy were hypotension (1.6%), asystole/cardiac arrest/PEA (1.2%), VT (1.1%), and cardiogenic shock (1%). Table 4 lists the most common (incidence *2%) adverse reactions during intravenous amiodarone therapy considered at least possibly drug-related. These data were collected in clinical trials involving 1836 patients with life-threatening VT/VF. Data from all assigned treatment groups are pooled because none of the adverse reactions appeared to be dose-related. Table 4: ADVERSE REACTIONS IN PATIENTS RECEIVING INTRAVENOUS AMIODARONE IN CONTROLLED AND OPEN-LABEL STUDIES (> 2% INCIDENCE) Study Event
Body as a whole Fever Cardiovascular System Bradycardia Congestive heart failure Heart arrest Hypotension Ventricular tachycardia Digestive System Liver function tests normal Nausea
Controlled Studies (n=814)
Open-Label Studies (n=1022)
Body as a whole
Body as a whole 13 (1.2%)
Body as a whole 37 (2.0%)
24 (2.9%) Cardiovascular 49 (6.0%) 18 (2.2%) 29 (3.5%) 165 (20.2%) 15 (1.8%) Digestive System 35 (4.2%) 29 (3.5%)
Cardiovascular 41 (4.0%) 21 (2.0%) 26 (2.5%) 123 (12.0%) 30 (2.9%) Digestive System 29 (2.8%) 43 (4.2%)
Cardiovascular 90 (4.9%) 39 (2.1%) 55 (2.9%) 288 (15.6%) 45 (2.4%) Digestive System 64 (3.4%) 72 (3.9%)
Other adverse reactions reported in less than 2% of patients receiving intravenous amiodarone in controlled and uncontrolled studies included the following: abnormal kidney function, atrial ﬁbrillation, diarrhea, increased ALT, increased AST, lung edema, nodal arrhythmia, prolonged QT interval, respiratory disorder, shock, sinus bradycardia, Stevens-Johnson syndrome, thrombocytopenia, VF, and vomiting. 6.2 Post-Marketing Experience The following adverse reactions have been identiﬁed during post-approval use of amiodarone. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Body as a Whole: anaphylactic/anaphylactoid reaction (including shock), fever
Pancreatic: pancreatitis Renal:l renal impairment, renal insufﬁciency, acute renal failure
Vascular: r vasculitis 7 DRUG INTERACTIONS Since amiodarone is a substrate for CYP3A and CYP2C8, drugs/substances that inhibit these isoenzymes may decrease the metabolism and increase serum concentration of amiodarone. Amiodarone inhibits p-glycoprotein and certain CYP450 enzymes, including CYP1A2, CYP2C9, CYP2D6, and CYP3A. This inhibition can result in unexpectedly high plasma levels of other drugs which are metabolized by those CYP450 enzymes or are substrates for p-glycoprotein. HMG-CoA reductase inhibitors that are CYP3A4 substrates in combination with amiodarone has been associated with reports of myopathy/rhabdomyolysis. Limit the dose of simvastatin in patients on amiodarone to 20 mg daily. Limit the daily dose of lovastatin to 40 mg. Lower starting and maintenance doses of other CYP3A4 substrates (e.g., atorvastatin) may be required. Some drugs/substances are known to accelerate the metabolism of amiodarone by stimulating the synthesis of CYP3A (enzyme induction). This may lead to low amiodarone serum levels and potential decrease in efﬁcacy. Fluoroquinolones, macrolide antibiotics, and azoles are known to cause QTc prolongation. There have been reports of QTc prolongation, with or without TdP, in patients taking amiodarone when ﬂuoroquinolones, macrolide antibiotics, or azoles were administered concomitantly. 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Category D Reproductive and teratology studies performed in rabbits and rats at doses of up to 100 mg/kg per day (about 1.4 times the maximum recommended human dose on a body surface area basis) revealed no evidence of embryotoxicity at 5 mg/kg and no teratogenicity was observed at any dosage in rabbits. Maternal toxicity and embryotoxicity were observed in rats in the 100 mg/kg group. Use NEXTERONE during pregnancy only if the potential beneﬁt to the mother justiﬁes the risk to the fetus. 8.2 Labor and Delivery It is not known whether the use of amiodarone during labor or delivery has any immediate or delayed adverse effects. 8.3 Nursing Mothers Amiodarone and one of its major metabolites, desethylamiodarone (DEA), are excreted in human milk, suggesting that breast-feeding could expose the nursing infant to a signiﬁcant dose of the drug. 8.4 Pediatric Use The safety and effectiveness of amiodarone in pediatric patients have not been established; therefore, the use of amiodarone in pediatric patients is not recommended. 8.5 Geriatric Use Clinical studies of amiodarone did not include sufﬁcient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Carefully consider dose selection in an elderly patient. 10 OVERDOSAGE There have been cases, some fatal, of amiodarone overdose. Effects of an inadvertent overdose of intravenous amiodarone include hypotension, cardiogenic shock, bradycardia, AV block, and hepatotoxicity. Treat hypotension and cardiogenic shock by slowing the infusion rate or with standard therapy: vasopressor drugs, positive inotropic agents, and volume expansion. Bradycardia and AV block may require temporary pacing. Monitor hepatic enzyme concentrations closely. Amiodarone is not dialyzable.
Baxter Healthcare Corporation Deerﬁeld, IL 60015 Baxter, Galaxy, Nexterone and the Sphere Graphic are trademarks of Baxter International Inc.
Cardiovascular: r hypotension (sometimes fatal), sinus arrest Dermatologic: toxic epidermal necrolysis (sometimes fatal), exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, skin cancer, pruritus, angioedema
Sourced from: 07-19-68-241 Rev. January 2012
Endocrine: syndrome of inappropriate antidiuretic hormone secretion (SIADH) Hematologic: pancytopenia, neutropenia, hemolytic anemia, aplastic anemia, thrombocytopenia, agranulocytosis, granuloma Hepatic: hepatitis, cholestatic hepatitis, cirrhosis Injection Site Reactions: pain, erythema, edema, pigment changes, venous thrombosis, phlebitis, thrombophlebitis, cellulitis, necrosis, and skin sloughing Musculoskeletal:l myopathy, muscle weakness, rhabdomyolysis
16 Operations & Management
Pharmacy Practice News • October 2013
DOOMSDAY continued from page 1
according to Dr. Brown. However, the job market for pharmacists is not keep ping pace, and by his estimatte, will accommodate only about 10,,000 to 12,000 new pharmacists peer year. Hence, by 2018, 3,000 grraduates (20%) per year will not find employment in their field. “I don’tt believe there currently is a need for more pharmacists,” Dr. Brown told d Pharmacy Practice News. “I think th he pipeline we’ve already got is more than enough.” h
Projections Don’t Equal Outcomes In a commentary in the same issue of AJPE (2013;77:91; doi: 10.5688/ ajpe77591), Katherine Knapp, PhD, and Jon C. Schommer, PhD, responded to
‘I don’t believe there currently is a need for more pharmacists. I think the pipeline we’ve already got is more than enough.’ —Daniel L. Brown, PharmD ““looming joblessn ness” might not haappen, including rissing demand for all health care servicees as the economy imprroves, and increasing retirement in the llarge cohort of pharmacists trained in the 1970s. Dr. Knapp, who is the dean of the Touro University California College of Pharmacy, in Vallejo, said in an interview that Dr. Brown’s commentary “was helpful in bringing to a wide audience data about the pharmacy
‘I continue to think that jobs are available, and I see that continuing for the foreseeable future.’ —Steven J. Martin, PharmD, BCPS Dr. Brown’s argument, asserting that “projections, even when based on the most solid evidence available, are not inescapable outcomes.” They outlined six scenarios under which Dr. Brown’s
education enterprise and the job market. It was not helpful because it tends to cause panic among students that there’s a bleak future for them.” She also faulted Dr. Brown for an “inac-
curate portrayal of the ability of the current pharmacy schools or accrediting agencies to prevent new schools from opening or schools from expanding. That clearly would be considered restraint of trade, and they could be sued under the Sherman Anti-Trust Act of 1890.” Furthermore, Dr. Knapp argued that Dr. Brown ignored factors other than an increase in graduates, such as the Great Recession. “I don’t agree that a glut [of pharmacists] is inevitable,” she said. Lucinda L. Maine, PhD, RPh, the executive vice president and CEO of the American Association of Colleges of Pharmacy (AACP), in Alexandria, Va., said in an interview: “The question is ‘is there any threat of significant unemployment facing our almost 300,000 licensed pharmacists now?’ I think that Dan’s answer was too unidimensional and simplistic.” An important unknown, Dr. Maine said, is the rate of expansion of the pharmacists’ patient care activities. Pharmacists will be doing more patient care in the future, and more of those positions will open up, she indicated.
Steven J. Martin, PharmD, BCPS, FCCP, FCCM, a professor and chairman, Department of Pharmacy Practice at the University of Toledo, Ohio, said Dr. Brown’s commentary “brought up a clear problem that we recognize in the academic world and that we’re seeing across the profession: that we have an increased number of graduates and that the job situation for those graduates has become tighter over the last few years.” However, he said, increasing demand for patient care services would continue to fuel job growth. Residency training, certificate programs, and MBA or MPH degrees will continue to make pharmacists “better able to be employed,” he suggested. “I continue to think that jobs are available, and I see that continuing for the foreseeable future.” —George Ochoa Drs. Brown, Knapp and Martin reported no relevant ﬁnancial conﬂicts of interest. Dr. Maine reported that a portion of AACP’s annual revenue comes from member institutions.
Web exclusive: Is the quality of pharmacy education another concern? See pharmacypracticenews.com for our continuing coverage.
Getting—and Staying—In Limited Distribution Networks Las Vegas—Given the rapid growth of specialty pharmacy—by 2016, seven of the top 10 branded drugs in the United States are expected to be specialty pharmaceuticals, according to industry experts—it’s not surprising that healthsystems continue to seek a share of this growing, lucrative market. Just last month, UHC, an alliance of nonprofit academic medical centers, announced that it is launching a new national specialty pharmacy program for its members. This initiative follows the 2012 launch of Excelera, a network of hospitals that continues to seek specialty contracts and, according to a top-level executive of the consortium, is ready to make an announcement regarding its progress this fall. Part of the success of these efforts will hinge not only on how well health systems can gain access to limited distribution networks for specialty drugs, but also how well they can deliver on data aggregation, patient and provider registration and other complex requirements these network contracts often carry. In fact, the price for not delivering on those contract requirements can be ejection from a network, according to
William Roth, founding partner of the health care consulting company Blue Fin Group. At the 2013 Armada Summit, Mr. Roth described the experience of a specialty pharmacy provider who was too slow to respond to a particularly important contract stipulation—the filling of newly prescribed medications. “Every script matters,” Mr. Roth said. “Even time to therapy matters. I have a large manufacturing client about to pull its product from specialty pharmacies because it takes six weeks to get to firsttime-to-fill. Manufacturers are intolerant of service-level deficiencies.” Another key to success in gaining access to—and staying in—specialty pharmacy networks is to understand the criteria that manufacturers use to decide whether to partner with a pharmacy services provider. Pharmacy networks, Mr. Roth said, are designed to reach a balance between patient access and manufacturer control. If a manufacturer feels that just one specialty pharmacy can allow for necessary patient access, it will choose that single pharmacy, achieve control and cut others out, he noted. “Manufacturers are going to take control of the channels,” Mr. Roth said.
“Every large manufacturer that has a self-administered product has a hub. If the pharmacies don’t do well with these products, they’ll simply take them out of the pharmacy and sell directly to the physician or the patient.” One trend that bodes well for large integrated health systems is the fact that the size of the typical specialty pharmacy network is growing, said pharmaceutical economics expert Adam Fein, PhD, the founder and president of Pembroke Consulting, a management advisory and business research firm. “The number of pharmacies that have the capabilities to be in limited networks continues to [expand],” he said. “URAC has accredited or is in the process of accrediting 80 specialty pharmacies. Typically, there are anywhere from five to 20 pharmacies in a manufacturer’s network, and the networks for non-orphan drug indications are starting to get bigger. It’s not appropriate for most of these products to be in a network of 60,000 retail pharmacies, but I do think manufacturers are feeling some pressure to open up their networks.” Another determining factor in network design, Mr. Roth said, is the competitive landscape among manufacturers. “If a
competitor has an exclusive network, so can you. If the competitor is wide open, that may influence you.” Traceability also is becoming a big selling point in specialty pharmacy networks. Mr. Roth described one client who uses serial IDs on their product in a limited network of specialty pharmacies. “When the 100 network pharmacies adjudicate claims, they do it with a serial ID linked back to the manufacturer,” he said. “I can know that there’s no fraud or abuse, because you can’t reuse my package.” This level of personalization, on all fronts, is likely to become more and more characteristic of specialty pharmacy networks, he said. “I have another client where the CEO of the company knows every single patient who’s on their drug. He knows if they take it. He knows if they’re a week late getting their infusion. That’s the level of depth involved. Try that with any primary care product!” The competitive jockeying for position to participate in specialty pharmacy networks ultimately is good for patients, noted Dr. Fein. “Competition will only improve the services that specialty pharmacies are providing.” —Gina Shaw
SAMSCA AÂ® (tolvaptan) tablets for oral use Brief Summary of Prescribing Information. Please see Full Prescribing Information for complete product information. 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\SRQDWUHPLDVHUXPVRGLXPP(T/RUOHVVPDUNHGK\SRQDWUHPLDWKDWLVV\PSWRPDWLFDQGKDVUHVLVWHGFRUUHFWLRQZLWKÃ€XLG restriction), including patients with heart failure and Syndrome of Inappropriate Antidiuretic Hormone (SIADH). Important Limitations: 3DWLHQWVUHTXLULQJLQWHUYHQWLRQWRUDLVHVHUXPVRGLXPXUJHQWO\WRSUHYHQWRUWRWUHDWVHULRXVQHXURORJLFDO V\PSWRPVVKRXOGQRWEHWUHDWHGZLWK6$06&$,WKDVQRWEHHQHVWDEOLVKHGWKDWUDLVLQJVHUXPVRGLXPZLWK6$06&$SURYLGHVD V\PSWRPDWLFEHQHÂ¿WWRSDWLHQWV CONTRAINDICATIONS: SAMSCA is contraindicated in the following conditions: 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: 3DWLHQWVZKRDUHXQDEOHWRDXWRUHJXODWHÃ€XLGEDODQFHDUHDW VXEVWDQWLDOO\LQFUHDVHGULVNRILQFXUULQJDQRYHUO\UDSLGFRUUHFWLRQRIVHUXPVRGLXPK\SHUQDWUHPLDDQGK\SRYROHPLD Hypovolemic hyponatremia:5LVNVDVVRFLDWHGZLWKZRUVHQLQJK\SRYROHPLDLQFOXGLQJFRPSOLFDWLRQVVXFKDVK\SRWHQVLRQDQG UHQDOIDLOXUHRXWZHLJKSRVVLEOHEHQHÂ¿WV Concomitant use of strong CYP 3A inhibitors:.HWRFRQD]ROHPJDGPLQLVWHUHGZLWKWROYDSWDQLQFUHDVHGWROYDSWDQH[SRVXUH E\IROG/DUJHUGRVHVZRXOGEHH[SHFWHGWRSURGXFHODUJHULQFUHDVHVLQWROYDSWDQH[SRVXUH7KHUHLVQRWDGHTXDWHH[SHULHQFHWR GHÂ¿QHWKHGRVHDGMXVWPHQWWKDWZRXOGEHQHHGHGWRDOORZVDIHXVHRIWROYDSWDQZLWKVWURQJ&<3$LQKLELWRUVVXFKDVFODULWKURP\FLQ NHWRFRQD]ROHLWUDFRQD]ROHULWRQDYLULQGLQDYLUQHOÂ¿QDYLUVDTXLQDYLUQHID]RGRQHDQGWHOLWKURP\FLQ Anuric patients: ,QSDWLHQWVXQDEOHWRPDNHXULQHQRFOLQLFDOEHQHÂ¿WFDQEHH[SHFWHG WARNINGS AND PRECAUTIONS: Too Rapid Correction of Serum Sodium Can Cause Serious Neurologic Sequelae (see BOXED WARNING): Osmotic demyelination syndrome is a risk associated with too rapid correction of hyponatremia (e.g., >12 mEq/L/24 hours). Osmotic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hours. Osmotic demyelination syndrome has been reported in association with SAMSCA therapy [see Adverse Reactions (6.2)]. Patients treated with SAMSCA should be monitored to assess serum sodium concentrations and neurologic status, especially GXULQJLQLWLDWLRQDQGDIWHUWLWUDWLRQ6XEMHFWVZLWK6,$'+RUYHU\ORZEDVHOLQHVHUXPVRGLXPFRQFHQWUDWLRQVPD\EHDWJUHDWHUULVNIRU WRRUDSLGFRUUHFWLRQRIVHUXPVRGLXP,QSDWLHQWVUHFHLYLQJ6$06&$ZKRGHYHORSWRRUDSLGDULVHLQVHUXPVRGLXPGLVFRQWLQXHRU LQWHUUXSWWUHDWPHQWZLWK6$06&$DQGFRQVLGHUDGPLQLVWUDWLRQRIK\SRWRQLFÃ€XLG)OXLGUHVWULFWLRQGXULQJWKHÂ¿UVWKRXUVRIWKHUDS\ ZLWK6$06&$PD\LQFUHDVHWKHOLNHOLKRRGRIRYHUO\UDSLGFRUUHFWLRQRIVHUXPVRGLXPDQGVKRXOGJHQHUDOO\EHDYRLGHG Liver Injury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see Adverse Reactions (6.1)]. Dehydration and Hypovolemia: 6$06&$WKHUDS\LQGXFHVFRSLRXVDTXDUHVLVZKLFKLVQRUPDOO\SDUWLDOO\RIIVHWE\Ã€XLGLQWDNH 'HK\GUDWLRQDQGK\SRYROHPLDFDQRFFXUHVSHFLDOO\LQSRWHQWLDOO\YROXPHGHSOHWHGSDWLHQWVUHFHLYLQJGLXUHWLFVRUWKRVHZKRDUH Ã€XLG UHVWULFWHG,QPXOWLSOHGRVHSODFHERFRQWUROOHGWULDOVLQZKLFKK\SRQDWUHPLFSDWLHQWVZHUHWUHDWHGZLWKWROYDSWDQWKHLQFLGHQFH RIGHK\GUDWLRQZDVIRUWROYDSWDQDQGIRUSODFHERWUHDWHGSDWLHQWV,QSDWLHQWVUHFHLYLQJ6$06&$ZKRGHYHORSPHGLFDOO\ VLJQLÂ¿FDQWVLJQVRUV\PSWRPVRIK\SRYROHPLDLQWHUUXSWRUGLVFRQWLQXH6$06&$WKHUDS\DQGSURYLGHVXSSRUWLYHFDUHZLWKFDUHIXO PDQDJHPHQWRIYLWDOVLJQVÃ€XLGEDODQFHDQGHOHFWURO\WHV)OXLGUHVWULFWLRQGXULQJWKHUDS\ZLWK6$06&$PD\LQFUHDVHWKHULVNRI GHK\GUDWLRQDQGK\SRYROHPLD3DWLHQWVUHFHLYLQJ6$06&$VKRXOGFRQWLQXHLQJHVWLRQRIÃ€XLGLQUHVSRQVHWRWKLUVW Co-administration with Hypertonic Saline: Concomitant use with hypertonic saline is not recommended. Drug Interactions: Other Drugs Affecting Exposure to Tolvaptan: CYP 3A Inhibitors:7ROYDSWDQLVDVXEVWUDWHRI&<3$&<3$LQKLELWRUVFDQOHDGWRDPDUNHGLQFUHDVHLQWROYDSWDQFRQFHQWUDWLRQV [see Dosage and Administration (2.3), Drug Interactions (7.1)]. 'RQRWXVH6$06&$ZLWKVWURQJLQKLELWRUVRI&<3$[see Contraindications (4.4)] DQGDYRLGFRQFRPLWDQWXVHZLWKPRGHUDWH&<3 $LQKLELWRUV CYP 3A Inducers: $YRLG FRDGPLQLVWUDWLRQ RI &<3 $ LQGXFHUV HJ 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 GHFUHDVHGHIIHFWLYHQHVV RI6$06&$WUHDWPHQW,IFRDGPLQLVWHUHGZLWK&<3$LQGXFHUVWKHGRVHRI6$06&$PD\QHHGWREH increased [see Dosage and Administration (2.3), Drug Interactions (7.1)]. P-gp Inhibitors: 7KH GRVH RI 6$06&$ PD\ KDYH WR EH UHGXFHG ZKHQ 6$06&$ LV FRDGPLQLVWHUHG ZLWK 3JS LQKLELWRUV HJ cyclosporine [see Dosage and Administration (2.3), Drug Interactions (7.1)]. Hyperkalemia or Drugs that Increase Serum Potassium: 7UHDWPHQWZLWKWROYDSWDQLVDVVRFLDWHGZLWKDQDFXWHUHGXFWLRQ RIWKH H[WUDFHOOXODU Ã€XLG YROXPH ZKLFK FRXOG UHVXOW LQ LQFUHDVHG VHUXP SRWDVVLXP 6HUXP SRWDVVLXP OHYHOV VKRXOG EH PRQLWRUHG DIWHU LQLWLDWLRQRIWROYDSWDQWUHDWPHQWLQSDWLHQWVZLWKDVHUXPSRWDVVLXP!P(T/DVZHOODVWKRVHZKRDUHUHFHLYLQJGUXJVNQRZQWR LQFUHDVHVHUXPSRWDVVLXPOHYHOV ADVERSE REACTIONS: Clinical Trials Experience: %HFDXVH FOLQLFDO WULDOV DUH FRQGXFWHG XQGHU ZLGHO\ YDU\LQJ FRQGLWLRQV DGYHUVH UHDFWLRQV UDWHV REVHUYHGLQWKHFOLQLFDOWULDOVRIDGUXJFDQQRWEHGLUHFWO\FRPSDUHGWRUDWHVLQWKHFOLQLFDOWULDOVRIDQRWKHUGUXJDQGPD\QRWUHÃ€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Â• PRUHWKDQSODFHER VHHQLQWZRGD\GRXEOHEOLQGSODFHERFRQWUROOHGK\SRQDWUHPLDWULDOVLQZKLFKWROYDSWDQZDVDGPLQLVWHUHGLQ titrated doses (15 mg to 60 mg once daily) were thirst, dry mouth, asthenia, constipation, pollakiuria or polyuria and hyperglycemia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able 1. Adverse Reactions (>2% more than placebo) in Tolvaptan-Treated Patients in Double-Blind, Placebo-Controlled Hyponatremia Trials System Organ Class MedDRA Preferred Term Gastrointestinal Disorders Dry mouth Constipation General Disorders and Administration Site Conditions 7KLUVWa Asthenia 3\UH[LD Metabolism and Nutrition Disorders Hyperglycemiab $QRUH[LDc Renal and Urinary Disorders Pollakiuria or polyuriad
Tolvaptan 15 mg/day-60 mg/day (N = 223) n (%)
(N = 220) n (%)
2 (1) 2 (1)
7KHIROORZLQJWHUPVDUHVXEVXPHGXQGHUWKHUHIHUHQFHG$'5LQ7DEOH a SRO\GLSVLD bGLDEHWHVPHOOLWXV cGHFUHDVHGDSSHWLWHdurine output increased, micturition, urgency, nocturia ,QDVXEJURXSRISDWLHQWVZLWKK\SRQDWUHPLD1 VHUXPVRGLXPP(T/ HQUROOHGLQDGRXEOHEOLQGSODFHERFRQWUROOHG WULDOPHDQGXUDWLRQRIWUHDWPHQWZDVPRQWKV RISDWLHQWVZLWKZRUVHQLQJKHDUWIDLOXUHWKHIROORZLQJDGYHUVHUHDFWLRQVRFFXUUHG LQ WROYDSWDQWUHDWHG SDWLHQWV DW D UDWH DW OHDVW JUHDWHU WKDQ SODFHER PRUWDOLW\ WROYDSWDQ SODFHER QDXVHD WROYDSWDQSODFHER WKLUVWWROYDSWDQSODFHER GU\PRXWKWROYDSWDQSODFHER DQGSRO\XULDRUSROODNLXULD U WROYDSWDQSODFHER Gastrointestinal bleeding in patients with cirrhosis: ,QSDWLHQWVZLWKFLUUKRVLVWUHDWHGZLWKWROYDSWDQLQWKHK\SRQDWUHPLDWULDOV
SAMSCAÂ® (tolvaptan) JDVWURLQWHVWLQDOEOHHGLQJZDVUHSRUWHGLQRXWRI WROYDSWDQWUHDWHGSDWLHQWVDQGRXWRI SODFHERWUHDWHGSDWLHQWV 7KHIROORZLQJDGYHUVHUHDFWLRQVRFFXUUHGLQRIK\SRQDWUHPLFF SDWLHQWVWUHDWHGZLWK SAMSCA and at a rate greater than placebo LQGRXEOHEOLQGSODFHERFRQWUROOHGWULDOV1 WROYDSWDQ1 SODFHER RULQRISDWLHQWVLQDQXQFRQWUROOHGWULDORISDWLHQWV with hyponatremia (N = 111) and are not mentioned elsewhere in the label: Blood and Lymphatic System Disorders: Disseminated LQWUDYDVFXODU FRDJXODWLRQ &DUGLDF 'LVRUGHUV ,QWUDFDUGLDF WKURPEXV YHQWULFXODU Â¿EULOODWLRQ ,QYHVWLJDWLRQV 3URWKURPELQ WLPH prolonged; Gastrointestinal Disorders: Ischemic colitis; Metabolism and Nutrition Disorders: Diabetic ketoacidosis; Musculoskeletal and Connective Tissue Disorders: Rhabdomyolysis; Nervous System: Cerebrovascular accident; Renal and Urinary Disorders: Urethral hemorrhage; Reproductive System and Breast Disorders (female): Vaginal hemorrhage; Respiratory, Thoracic, and Mediastinal Disorders: Pulmonary embolism, respiratory failure; Vascular disorder: Deep vein thrombosis. Postmarketing Experience: 7KHIROORZLQJDGYHUVHUHDFWLRQVKDYHEHHQLGHQWLÂ¿HGGXULQJSRVWDSSURYDOXVHRI6$06&$%HFDXVH WKHVHUHDFWLRQVDUHUHSRUWHGYROXQWDULO\IURPDSRSXODWLRQRIDQXQNQRZQVL]HLWLVQRWDOZD\VSRVVLEOHWRUHOLDEO\HVWLPDWHWKHLU IUHTXHQF\RUHVWDEOLVKDFDXVDOUHODWLRQVKLSWRGUXJH[SRVXUH Neurologic: 2VPRWLFGHP\HOLQDWLRQV\QGURPH Investigations: Hypernatremia 5HPRYDO RI H[FHVV IUHH ERG\ ZDWHU LQFUHDVHV VHUXP RVPRODOLW\ DQG VHUXP VRGLXP FRQFHQWUDWLRQV $OO SDWLHQWV WUHDWHG ZLWK WROYDSWDQHVSHFLDOO\WKRVHZKRVHVHUXPVRGLXPOHYHOVEHFRPHQRUPDOVKRXOGFRQWLQXHWREHPRQLWRUHGWRHQVXUHVHUXPVRGLXP UHPDLQVZLWKLQQRUPDOOLPLWV,IK\SHUQDWUHPLDLVREVHUYHGPDQDJHPHQWPD\LQFOXGHGRVHGHFUHDVHVRULQWHUUXSWLRQRIWROYDSWDQ WUHDWPHQWFRPELQHGZLWKPRGLÂ¿FDWLRQRIIUHHZDWHULQWDNHRULQIXVLRQ'XULQJFOLQLFDOWULDOVRIK\SRQDWUHPLFSDWLHQWVK\SHUQDWUHPLD ZDV UHSRUWHG DV DQ DGYHUVH HYHQW LQ RI SDWLHQWV UHFHLYLQJ WROYDSWDQ YV RI SDWLHQWV UHFHLYLQJ SODFHER DQDO\VLV RI ODERUDWRU\YDOXHVGHPRQVWUDWHGDQLQFLGHQFHRIK\SHUQDWUHPLDRILQSDWLHQWVUHFHLYLQJWROYDSWDQYVLQSDWLHQWVUHFH I LYLQJ placebo. DRUG INTERACTIONS: Effects of Drugs on Tolvaptan: Ketoconazole and Other Strong CYP 3A Inhibitors: 6$06&$LVPHWDEROL]HGSULPDULO\E\&<3$.HWRFRQD]ROHLVDVWURQJ LQKLELWRURI&<3$DQGDOVRDQLQKLELWRURI3JS&RDGPLQLVWUDWLRQRI6$06&$DQGNHWRFRQD]ROHPJGDLO\UHVXOWVLQDIROG LQFUHDVH LQ H[SRVXUH WR WROYDSWDQ &RDGPLQLVWUDWLRQ RI 6$06&$ ZLWK PJ NHWRFRQD]ROH GDLO\ RU ZLWK RWKHU VWURQJ &<3 $ LQKLELWRUVHJFODULWKURP\FLQLWUDFRQD]ROHWHOLWKURP\FLQVDTXLQDYLUQHOÂ¿QDYLUULWRQDYLUDQGQHID]RGRQH DWWKHKLJKHVWW ODEHOHG GRVHZRXOGEHH[SHFWHGWRFDXVHDQHYHQJUHDWHULQFUHDVHLQWROYDSWDQH[SRVXUH7KXV6$06&$DQGVWURQJ&<3$LQKLELWRUV should not be co-administered [see Dosage and Administration (2.3) and Contraindications (4.4)]. Moderate CYP 3A Inhibitors: 7KHLPSDFWRIPRGHUDWH&<3$LQKLELWRUVHJHU\WKURP\FLQÃ€XFRQD]ROHDSUHSLWDQWGLOWLD]HP DQGYHUDSDPLO RQWKHH[SRVXUHWRFRDGPLQLVWHUHGWROYDSWDQKDVQRWEHHQDVVHVVHG$VXEVWDQWLDOLQFUHDVHLQWKHH[SRVXUHWR WROYDSWDQZRXOGEHH[SHFWHGZKHQ6$06&$LVFRDGPLQLVWHUHGZLWK PRGHUDWH&<3$LQKLELWRUV&RDGPLQLVWUDWLRQRI6$06&$ ZLWKPRGHUDWH&<3$LQKLELWRUVVKRXOGWKHUHIRUHJHQHUDOO\EHDYRLGHG [see Dosage and Administration (2.3) and Warnings and Precautions (5.5)]. Grapefruit Juice: &RDGPLQLVWUDWLRQRIJUDSHIUXLWMXLFHDQG6$06&$UHVXOWVLQDIROGLQFUHDVHLQH[SRVXUH WR WROYDSWDQ [see Dose and Administration (2.3) and Warnings and Precautions (5.5)]. P-gp Inhibitors: Reduction in the dose of SAMSCA may be required in patients concomitantly treated with P-gp inhibitors, such as e.g., cyclosporine, based on clinical response [see Dose and Administration (2.3) and Warnings and Precautions (5.5)]. Rifampin and Other CYP 3A Inducers: 5LIDPSLQLVDQLQGXFHURI&<3$DQG3JS&RDGPLQLVWUDWLRQRIULIDPSLQDQG6$06&$UHGXFHVH[SRVXUHWRWROYDSWDQE\ I 7KHUHIRUH WKH H[SHFWHG FOLQLFDO HIIHFWV RI 6$06&$ LQ WKH SUHVHQFH RI ULIDPSLQ DQG RWKHU LQGXFHUV HJ ULIDEXWLQ ULIDSHQWLQ EDUELWXUDWHV SKHQ\WRLQ FDUEDPD]HSLQH DQG 6W -RKQÂ¶V :RUW PD\\ QRW EH REVHUYHG DW WKH XVXDO GRVH OHYHOV RI 6$06&$ 7KH GRVHRI6$06&$PD\KDYHWREHLQFUHDVHG[Dosage and Administration (2.3) and Warnings and Precautions (5.5)]. Lovastatin, Digoxin, Furosemide, and Hydrochlorothiazide: &RDGPLQLVWUDWLRQRIORYDVWDWLQGLJR[LQIXURVHPLGHDQGK\GURFKORURWKLD]LGH ZLWK6$06&$KDVQRFOLQLFDOO\UHOHYDQWLPSDFWRQWKHH[SRVXUHWRWROYDSWDQ Effects of Tolvaptan on Other Drugs: Digoxin: 'LJR[LQLVD3JSVXEVWUDWH&RDGPLQLVWUDWLRQRI6$06&$ZLWKGLJR[LQLQFUHDVHG GLJR[LQ$8& E\ DQG &PD[ E\ Warfarin, Amiodarone, Furosemide, and Hydrochlorothiazide: Co-administration RI WROYDSWDQ GRHV QRW DSSHDU WR DOWHU WKH SKDUPDFRNLQHWLFV RI ZDUIDULQ IXURVHPLGH K\GURFKORURWKLD]LGH RU DPLRGDURQH RU LWV DFWLYHPHWDEROLWHGHVHWK\ODPLRGDURQH WRDFOLQLFDOO\VLJQLÂ¿FDQWGHJUHH Lovastatin: 6$06&$LVDZHDNLQKLELWRURI&<3$&R DGPLQLVWUDWLRQRIORYDVWDWLQDQG6$06&$LQFUHDVHVWKHH[SRVXUHWRORYDVWDWLQDQGLWVDFWLYHPHWDEROLWHORYDVWDWLQÈ•K\GUR[\DFLGE\ IDFWRUVRIDQGUHVSHFWLYHO\7KLVLVQRWDFOLQLFDOO\UHOHYDQWFKDQJH Pharmacodynamic Interactions: 7ROYDSWDQ SURGXFHV D JUHDWHU KRXU XULQH YROXPHH[FUHWLRQ UDWH WKDQ GRHV IXURVHPLGH RU K\GURFKORURWKLD]LGH &RQFRPLWDQW DGPLQLVWUDWLRQ RI WROYDSWDQ ZLWK IXURVHPLGH RU K\GURFKORURWKLD]LGH UHVXOWV LQ D KRXU XULQH YROXPHH[FUHWLRQUDWHWKDWLVVLPLODUWRWKHUDWHDIWHUWROYDSWDQDGPLQLVWUDWLRQDORQH$OWKRXJKVSHFLÂ¿FLQWHUDFWLRQVWXGLHVZHUHQRW SHUIRUPHG LQ FOLQLFDO VWXGLHV WROYDSWDQ ZDV XVHG FRQFRPLWDQWO\ \ ZLWK EHWDEORFNHUV DQJLRWHQVLQ UHFHSWRU EORFNHUV DQJLRWHQVLQ FRQYHUWLQJHQ]\PHLQKLELWRUVDQGSRWDVVLXPVSDULQJGLXUHWLFV$GYHUVHUHDFWLRQVRIK\SHUNDOHPLDZHUHDSSUR[LPDWHO\KLJKHU ZKHQ WROYDSWDQ ZDV DGPLQLVWHUHG ZLWK DQJLRWHQVLQ UHFHSWRU EORFNHUV DQJLRWHQVLQ FRQYHUWLQJ HQ]\PH LQKLELWRUV DQG SRWDVVLXP VSDULQJ GLXUHWLFV FRPSDUHG WR DGPLQLVWUDWLRQ RI WKHVH PHGLFDWLRQV ZLWK SODFHER 6HUXP SRWDVVLXP OHYHOV VKRXOG EH PRQLWRUHG during concomitant drug therapy. As a V2 UHFHSWRUDQWDJRQLVWWROYDSWDQPD\LQWHUIHUHZLWKWKH92DJRQLVWDFWLYLW\RIGHVPRSUHVVLQ G'$93 ,QDPDOHVXEMHFWZLWKPLOG9RQ:LOOHEUDQGY: GLVHDVHLQWUDYHQRXVLQIXVLRQRIG'$93KRXUVDIWHUDGPLQLVWUDWLRQ RIRUDOWROYDSWDQGLGQRWSURGXFHWKHH[SHFWHGLQFUHDVHVLQY: )DFWRU$QWLJHQRU)DFWRU9,,,DFWLYLW\,WLVQRWUHFRPPHQGHGWR administer SAMSCA with V2 agonist. USE IN SPECIFIC POPULATIONS: 7KHUHLVQRQHHGWRDGMXVWGRVHEDVHGRQDJHJHQGHUUDFHRUFDUGLDFIXQFWLRQ[see Clinical Pharmacology (12.3)]. Pregnancy: Pregnancy Category C. 7KHUHDUHQRDGHTXDWHDQGZHOOFRQWUROOHGVWXGLHVRI6$06&$XVHLQSUHJQDQWZRPHQ,Q DQLPDOVWXGLHVFOHIWSDODWHEUDFK\PHOLDPLFURSKWKDOPLDVNHOHWDOPDOIRUPDWLRQVGHFUHDVHGIHWDOZHLJKWGHOD\HGIHWDORVVLÂ¿FDWLRQ DQGHPEU\RIHWDOGHDWKRFFXUUHG6$06&$VKRXOGEHXVHGGXULQJSUHJQDQF\RQO\LIWKHSRWHQWLDOEHQHÂ¿WMXVWLÂ¿HVWKHSRWHQWLDOULVN WRWKHIHWXV,QHPEU\RIHWDOGHYHORSPHQWVWXGLHVSUHJQDQWUDWVDQGUDEELWVUHFHLYHGRUDOWROYDSWDQGXULQJRUJDQRJHQHVLV5DWV UHFHLYHGWRWLPHVWKHPD[LPXPUHFRPPHQGHGKXPDQGRVH05+' RIWROYDSWDQRQDERG\VXUIDFHDUHDEDVLV 5HGXFHG fetal weights and delayed fetal RVVLÂ¿FDWLRQRFFXUUHGDWWLPHVWKH05+'6LJQVRIPDWHUQDOWR[LFLW\UHGXFWLRQLQERG\Zeight JDLQDQGIRRGFRQVXPSWLRQ RFFXUUHGDWDQGWLPHVWKH05+':KHQSUHJQDQWUDEELWVUHFHLYHGRUDOWROYDSWDQDWWR times the MRHD (on a body surface area basis), there were reductions in maternal body weight gain and food consumption at all GRVHVDQGLQFUHDVHGDERUWLRQVDWWKHPLGDQGKLJKGRVHVDERXWDQGWLPHVWKH05+' $WWLPHVWKH05+'WKHUHZHUH increased rates of embryo-fetal death, fetal microphthalmia, open eyelids, cleft palate, brachymelia and skeletal malformations [see Nonclinical Toxicology (13.3)]. Labor and Delivery: 7KHHIIHFWRI6$06&$RQODERUDQGGHOLYHU\LQKXPDQVLVXQNQRZQ Nursing Mothers: ,WLVQRWNQRZQZKHWKHU6$06&$LVH[FUHWHGLQWRKXPDQPLON7ROYDSWDQLVH[FUHWHGLQWRWKHPLONRIODFWDWLQJ UDWV %HFDXVH PDQ\ GUXJV DUH H[FUHWHG LQWR KXPDQ PLON DQG EHFDXVH RI WKH SRWHQWLDO IRU VHULRXV DGYHUVH UHDFWLRQV LQ QXUVLQJ infants from SAMSCA, a decision should be made to discontinue nursing or SAMSCA, taking into consideration the importance of SAMSCA to the mother. Pediatric Use: 6DIHW\DQGHIIHFWLYHQHVVRI6$06&$LQSHGLDWULFSDWLHQWVKDYHQRWEHHQHVWDEOLVKHG Geriatric Use:2IWKHWRWDOQXPEHURIK\SRQDWUHPLFVXEMHFWVWUHDWHGZLWK6$06&$LQFOLQLFDOVWXGLHVZHUHDQGRYHUZKLOH ZHUHDQGRYHU1RRYHUDOOGLIIHUHQFHVLQVDIHW\RUHIIHFWLYHQHVVZHUHREVHUYHGEHWZHHQWKHVHVXEMHFWVDQG\RXQJHUVXEMHFWV DQGRWKHUUHSRUWHGFOLQLFDOH[SHULHQFHKDVQRWLGHQWLÂ¿HGGLIIHUHQFHVLQUHVSRQVHVEHWZHHQWKHHOGHUO\DQG\RXQJHUSDWLHQWVEXWJUHDWHU VHQVLWLYLW\RIVRPHROGHULQGLYLGXDOVFDQQRWEHUXOHGRXW,QFUHDVLQJDJHKDVQRHIIHFWRQWROYDSWDQSODVPDFRQFHQWUDWLRQV Use in Patients with Hepatic Impairment: 0RGHUDWHDQGVHYHUHKHSDWLFLPSDLUPHQWGRQRWDIIHFWH[SRVXUHWRWROYDSWDQWRDFOLQLFDOO\ UHOHYDQWH[WHQW1RGRVHDGMXVWPHQWRIWROYDSWDQLVQHFHVVDU\$YRLGXVHRIWROYDSWDQLQSDWLHQWVZLWKXQGHUO\LQJOLYHUGLVHDVH Use in Patients with Renal Impairment: 1RGRVHDGMXVWPHQWLVQHFHVVDU\EDVHGRQUHQDOIXQFWLRQ7KHUHDUHQRFOLQLFDOWULDO GDWDLQSDWLHQWVZLWK&U&OP/PLQDQGEHFDXVHGUXJHIIHFWVRQVHUXPVRGLXPOHYHOVDUHOLNHO\ORVWDWYHU\ORZOHYHOVRIUHQDO IXQFWLRQXVHLQSDWLHQWVZLWKD&U&OP/PLQLVQRWUHFRPPHQGHG1REHQHÂ¿WFDQEHH[SHFWHGLQSDWLHQWVZKRDUHDQXULF[see Contraindications 4.5) and Clinical Pharmacology (12.3)]. Use in Patients with Congestive Heart Failure: 7KHH[SRVXUHWRWROYDSWDQLQSDWLHQWVZLWKFRQJHVWLYHKHDUWIDLOXUHLVQRWFOLQLFDOO\ UHOHYDQWO\LQFUHDVHG1RGRVHDGMXVWPHQWLVQHFHVVDU\ OVERDOSAGE:6LQJOHRUDOGRVHVXSWRPJDQGPXOWLSOHGRVHVXSWRPJ RQFHGDLO\IRUGD\VKDYHEHHQZHOOWROHUDWHGLQ VWXGLHVLQKHDOWK\VXEMHFWV7KHUHLVQRVSHFLÂ¿FDQWLGRWHIRUWROYDSWDQLQWR[LFDWLRQ7KHVLJQVDQGV\PSWRPVRIDQDFXWHRYHUGRVH FDQ EH DQWLFLSDWHG WR EH WKRVH RI H[FHVVLYH SKDUPDFRORJLF HIIHFW D ULVH LQ VHUXP VRGLXP FRQFHQWUDWLRQ SRO\XULD WKLUVW DQG GHK\GUDWLRQK\SRYROHPLD7KHRUDO/'RIWROYDSWDQLQUDWVDQG GRJVLV!PJNJ1RPRUWDOLW\ZDVREVHUYHGLQUDWVRUGRJV IROORZLQJ VLQJOH RUDO GRVHV RI PJNJ PD[LPXP IHDVLEOH GRVH $ VLQJOH RUDO GRVH RI PJNJ ZDV OHWKDO LQ PLFH DQG V\PSWRPVRIWR[LFLW\LQDIIHFWHGPLFHLQFOXGHGGHFUHDVHGORFRPRWRUDFWLYLW\VWDJJHULQJJDLWWUHPRUDQGK\SRWKHUPLD ,IRYHUGRVHRFFXUVHVWLPDWLRQRIWKHVHYHULW\RISRLVRQLQJLVDQLPSRUWDQWÂ¿UVWVWHS$WKRURXJKKLVWRU\DQGGHWDLOVRIRYHUGRVHVKRXOG EHREWDLQHGDQGDSK\VLFDOH[DPLQDWLRQVKRXOGEHSHUIRUPHG7KHSRVVLELOLW\RIPXOWLSOHGUXJLQYROYHPHQWVKRXOGEHFRQVLGHUHG 7UHDWPHQW VKRXOG LQYROYH V\PSWRPDWLF DQG VXSSRUWLYH FDUH ZLWK UHVSLUDWRU\ (&* DQG EORRG SUHVVXUH PRQLWRULQJ DQG ZDWHU HOHFWURO\WHVXSSOHPHQWVDVQHHGHG$SURIXVHDQGSURORQJHGDTXDUHVLVVKRXOGEHDQWLFLSDWHGZKLFKLIQRWPDWFKHGE\RUDOÃ€XLG LQJHVWLRQVKRXOGEHUHSODFHGZLWKLQWUDYHQRXVK\SRWRQLFÃ€XLGV ZKLOHFORVHO\PRQLWRULQJHOHFWURO\WHVDQGÃ€XLGEDODQFH (&*PRQLWRULQJVKRXOGEHJLQLPPHGLDWHO\DQGFRQWLQXHXQWLO(&*SDUDPHWHUVDUHZLWKLQQRUPDOUDQJHV'LDO\VLVPD\QRWEH HIIHFWLYHLQUHPRYLQJWROYDSWDQEHFDXVHRILWVKLJKELQGLQJDIÂ¿QLW\IRUKXPDQSODVPDSURWHLQ! &ORVHPHGLFDOVXSHUYLVLRQ DQG PRQLWRULQJVKRXOGFRQWLQXHXQWLOWKHSDWLHQWUHFRYHUV PATIENT COUNSELING INFORMATION: $V D SDUW RI SDWLHQW FRXQVHOLQJ KHDOWKFDUH SURYLGHUV PXVW UHYLHZ WKH 6$06&$ 0HGLFDWLRQ*XLGHZLWKHYHU\SDWLHQW[see FDA-Approved Medication Guide (17.3)]. Concomitant Medication: $GYLVHSDWLHQWVWRLQIRUPWKHLUSK\VLFLDQLIWKH\DUHWDNLQJRUSODQWRWDNHDQ\SUHVFULSWLRQRURYHUWKH U counter drugs since there is a potential for interactions.Strong and Moderate CYP 3A inhibitors and P-gp inhibitors: $GYLVH SDWLHQWVWRLQIRUPWKHLUSK\VLFLDQLIWKH\XVHVWURQJHJNHWRFRQD]ROHLWUDFRQD]ROHFODULWKURP\FLQWHOLWKURP\FLQQHOÂ¿QDYLUVDTXLQDYLU LQGLQDYLUULWRQDYLU RUPRGHUDWH&<3$LQKLELWRUVHJDSUHSLWDQWHU\WKURP\FLQGLOWLD]HPYHUDSDPLOÃ€XFRQD]RO RU3JSLQKLELWRUV (e.g., cyclosporine) [see Dosage and Administration (2.3), Contraindications (4.4), Warnings and Precautions (5.5) and Drug Interactions (7.1)]. Nursing: $GYLVHSDWLHQWVQRWWREUHDVWIHHGDQLQIDQWLIWKH\DUHWDNLQJ6$MSCA >VHH8VH,Q6SHFLÂ¿F3RSXODWLRQV @ )RUPRUHLQIRUPDWLRQDERXW6$06&$FDOORUJRWR ZZZVDPVFDFRP 0DQXIDFWXUHGE\2WVXND3KDUPDFHXWLFDO&R/WG7RN\R-DSDQ 'LVWULEXWHGDQGPDUNHWHGE\2WVXND$PHULFD3KDUPDFHXWLFDO,QF5RFNYLOOH0' SAMSCA is a registered g trademark of Otsuka Pharmaceutical Co., Ltd., Tokyo, 101-8535 Japan
86/%5HY Â© 2013 Otsuka Pharmaceutical Co., Ltd.
FREE VVV2ATER Order SAMSCA® (tolvaptan) CLEARANCE
Unique oral treatment for clinically significant hypervolemic and euvolemic hyponatremia
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 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, and anuric patients. Warnings and Precautions: • 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 • SAMSCA can cause serious and potentially fatal liver injury. Avoid use in patients with underlying liver disease, including cirrhosis, because the ability to recover may be impaired. Limit duration of therapy with SAMSCA to 30 days • 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 • Co-administration with hypertonic saline is not recommended • Avoid use with: CYP 3A inhibitors and CYP 3A inducers. The dose of SAMSCA may have to be reduced if co-administered with P-gp inhibitors • Monitor serum potassium levels in patients with a serum potassium >5 mEq/L and in patients receiving drugs known to increase serum potassium levels Gastrointestinal Bleeding in Patients with Cirrhosis: In patients with cirrhosis in the hyponatremia trials, GI bleeding was reported in 10% of tolvaptan-treated patients vs 2% for placebo. Commonly Observed Adverse Reactions: (SAMSCA incidence ≥5% more than placebo, respectively): 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%).
Please see Brief Summary of FULL PRESCRIBING INFORMATION, including Boxed WARNING, on previous page. For more information, visit SAMSCA.com or call 1-877-726-7220. 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.
©2013 Otsuka America Pharmaceutical, Inc.
Operations & Management 19
Pharmacy Practice News • October 2013
Leadership in Action
Is It Time To Change Your Thinking? W
e often learn our most valuable lessons from children, so here’s an instructive tale of a grade school that made an unexpected discovery about the nature of boundaries and the effect they have on our behavior. The school had a large playground surrounded by a chain-link fence. The children enjoyed playing on nearly every corner of that enclosure, using almost— but not quite—all of the available space for their activities. Still, someone was concerned that the fence was too enclosing and would undermine the children’s social development, so they convinced the school to remove the fence. Lo and behold, rather than encourage even more freedom and social engagement, the children no longer played to the perimeter of the playground area but tended to congregate more toward the middle of the field of play. The boundary of the fence was in fact security for the children. Without it, they tended to huddle, maybe not in fear but with a degree of insecurity that held them back from realizing their full potential. We too need boundaries as adult professionals in order to perform to our maximum potential.
thinking at higher levels of brain function to solve our current problems in health care. I continue to be amazed the more I learn about neuroplasticity and the ability to expand our thinking. When people are engaged at high levels of problem solving and thinking, powerful results are possible. Creating this type of culture in an organization is liberating and exciting. This type of culture allows people to grow professionally. There is continual learning and constant adaptation to a changing environment. In health care today, we are learning to think differently in a risk-sharing environment that measures quality outcomes versus the feefor-service mentality that drives an overuse of resources without attention to quality of care. I constantly think about the role of pharmacy in these new environments. We are the professionals who need to think these pharmacy roles through and sell them to the health community at large. Others are not going to think the way pharmacists think! We need to remember that our perspective of health care is unique. Do others sense the power of our thinking as pharmacists?
The Nature of Boundaries
Creating the Right Emotional Climate
In last month’s column, we began to explore the manager’s responsibility for setting clear boundaries within his or her department. As Henry Cloud said in his book “Boundaries for Leaders” (HarperCollins, 2013), “Boundaries are made up of two essential things; what you create and what you allow.” Giving employees boundaries sets expectations and actually frees people to be creatively empowered. We must ensure that the energy of the department is focused on what is important to drive results, while limiting distractions, intrusions and toxic interactions. Clarity leads to attention and attention leads to results.
The Higher Orders of Thinking For this strategy to work, the manager needs to create a climate that challenges people to “figure things out in the best way possible,” rather than dictating to them with a “top-down” approach. During this process, the manager also notes what is not important and steers people back on track if they get distracted. But it’s also crucial to give employees the space they need to work through the challenges they are given. In fact, studies have shown that when people are given the space to create their own pathways to success—with guidance, of course—they create new neural pathways that lead to higher levels of thinking. Why is this process so important? Because we need transformational
Is it your experience, as it is mine, that people have trouble moving forward and achieving their professional goals when they are distracted by personal feelings and emotions at work? People think best when they are not stressed, afraid or depressed. Therefore, it is incumbent on us as leaders to create a positive emotional climate within our depart-
ments. I have worked in an atmosphere of fear as people and/or their jobs were being eliminated all around me, until it eventually included me. Stress or fear also can come from public humiliation. In my case, I have seen that exemplified by a senior executive at a health care organization who was a screamer. I bore the brunt of that outburst once and witnessed it in public meetings often. If you have been on the receiving end, you understand how fear creates inaction; you become afraid to move forward for fear of being yelled at or being asked, “who gave you the authority to make that decision?” Now some of these may be extreme examples that you may not have experienced. However, as leaders we need to consider the more subtle ways in which we can negatively influence others. Perhaps our tone of voice has been overly critical. When others perceive aggressive, angry or harsh tones that are overly critical, it can cause a shift in brain function. This is often called an “Amygdala Hijack.” This moves our thinking to the emotional center of our brain and away from the prefrontal cortex where higher thinking takes place. As we were taught in school, this is the flight-or-fight response. Stress and fear cause people to shift to the limbic system and move away from the higher cortical areas that are responsible for logic, problem solving, analysis, planning, prioritization, working memory and so on—in short, the area in which we want our people to be functioning. As Henry Cloud said, “when the options for ‘fight-or-flight’ aren’t available, it’s as if a giant ‘freeze button’ gets hit. We
‘When people are given the space to create their own pathways to success ... they create new neural pathways that lead to higher levels of thinking.’
“Leadership in Action” is authored by Ernest R. Anderson Jr., MS, RPh, of Brockton, Mass. Mr. Anderson welcomes your input on leadership issues, at anderson489@ comcast.net.
Ernest R. Anderson Jr., MS, RPh
shut down entirely. We get paralyzed.” How do people respond in this mode of thinking? They usually are defensive or angry or they avoid conflict by avoiding the instigator. Often this negative type of atmosphere is palpable in a department, hospital or even health system.
Be Positive! Building positive relationships with co-workers or subordinates encourages people to use their prefrontal cortex, enabling them to maximize problem solving and to be open to new ideas. In nearly all cases I’ve seen, this type of workplace environment, given enough time, improves efficiency and productivity. Remember, positive attitudes are contagious; people flourish under a positive leader who is fostering a climate conducive to using and expanding the intellectual capacity and abilities of everyone. Does that mean we allow people to fly off into tangential areas because we do not want to rein them in? Absolutely not! Our job is to create the boundaries in which to operate. We need to combine a goal-oriented, yet relational, approach. We care about the people and have a work ethic that requires drive, expectations and discipline. Structure is important. Lack of structure creates its own type of stress. If leaders are too aggressively pursuing results with no focus on their emotional tone to the employees, employees can have a brain freeze and shut down. So we must give direction, structure, accountability and expectations that drive toward the goals in a way that does not create stress. This is where our tone is so important, where remaining calm and showing empathy (when appropriate) can make a huge difference in helping us build and maintain positive relationships. Another way I often teach the approach is to “be hard on the issue but soft on the people.” In other words, never belittle or attack the person, but address the issue. The time you take to take a deep breath, show restraint and strike the right balance between firmness and support will pay off in dedicated workers who enjoy being in your department and reaching common goals set forth under your leadership. Good luck! ■
Pharmacy Practice News • October 2013
IPPS RULE continued from page 1
likely be expanded to include readmissions for other medical conditions. CMS also included a safe harbor in its readmissions payment policy by adding 15 new discharge status codes for planned readmissions that do not incur any federal pay cuts. But that cushion should not detract hospital pharmacies from acting now to shore up efforts to stay under the CMS readmissions ceiling, according to Ernie Anderson
Jr., MS, RPh, a Brockton, Mass.–based health care consultant. “Pharmacy can play a key role here, because roughly half of all readmissions are medicationrelated,” Mr. Anderson said. “Most hospitals have already organized or are forming multidisciplinary readmission committees. Pharmacists should have a seat at the table.”
Improving Transition of Care Pharmacists need to focus more on the patient discharge process and transition of care issues to improve medi-
‘Academic medical centers and community hospitals may not have the staff available to devote to discharge. But they can still improve.’ —Ali McBride, PharmD cation adherence and reconciliation, Mr. Anderson said. “You hear horror stories all the time about patients who got readmitted because they didn’t take their medications properly.” Discharge counseling, when pharmacists make sure patients and their care-
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givers understand how to manage their medications, and post-discharge followup calls to patients in their homes are two proven ways to improve medication adherence, he noted. If it’s not possible for a pharmacist to contact all discharged patients, he suggested using an algorithm to determine which patients are most likely to be readmitted. The pharmacist can then call those patients at home. Yet another component to preventing readmissions due to medication mishaps would be to better use retail pharmacies in the community. “Pharmacies like CVS and Walgreens could conduct brown-bag reviews of the patients who spend the most on medications,” Mr. Anderson said. “Their local pharmacists may pick up on problems that otherwise wouldn’t come to light.” He acknowledged, however, that “no good consistentt mechanism exists to bridge the gap between the health system and the retail pharmacy.” Still, “professionals from these two traditional silos have started to have some dialogue to determine how this can be remedied.” For 340B hospitals, there may be a built-in solution for bolstering patient care and reducing hospital readmissions. These facilities can work with retail pharmacies to be their “contract pharmacy” under the federal drug discount program, Mr. Anderson noted. “This relationship can help these entities bridge care gaps and manage patients’ medications collaboratively,” he said.
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Although some hospital pharmacies already are deeply involved with the discharge process, other institutions will have a tougher time making changes. “Larger hospitals are where you may see more discharge-based interventions,” said Ali McBride, PharmD, MS, BCPS, the clinical coordinator of Hematology and Oncology at the University of Arizona Cancer Center, in Tucson. “Academic medical centers and community hospitals may not have the staff available to devote to discharge. But they can still improve. For example, they may be able to partner with social workers to help make sure patients have their medications from the local retail pharmacy already waiting for them when they return home.” However, pharmacists should be careful with relying too heavily on nurses or social workers during the discharge process, Mr. Anderson said. “They just don’t have the same knowledge base as pharmacists. Often, they only know about the products on the hospital formulary.
Pharmacy Practice News • October 2013
Hospital-Acquired Conditions Among Other IPPS Pains
lthough hospital readmission reduction is a central goal under the updated Inpatient Prospective Payment System (IPPS), other components need to be heeded in order to dampen the fiscal pain that may result from the payment changes. These include a clarification of how a patient’s admission status affects reimbursement, the process for implementing the new hospital-acquired conditions (HAC) reduction program, and a refinement of the hospital valuebased purchasing (VBP) incentive program. Here’s a look at some of the changes: Hospital–acquired conditions: The Affordable Care Act (ACA) requires the Centers for Medicare & Medicaid Services (CMS) to establish a program to improve patient safety by imposing financial penalties on hospitals that perform poorly with regard to HACs. The conditions cited in the updated policy include everything from pressure ulcers, and foreign objects left in the body, to central line–associated bloodstream infection and catheter-associated urinary tract infection. Under the program, hospitals that rank in the lowest-performing quartile of HAC will be paid 99% of what they otherwise would have been paid under IPPS, beginning in fiscal year 2015. “The spread of infection in hospitals is well-documented,” said Ernie Anderson, MS, RPh, a Brockton, Mass.-based independent healthcare consultant. “But now the government is saying to hospitals: ‘Hey,
So when a patient says to them, ‘I have ramipril in my medicine chest at home, and they sent me home with lisinopril,’ a non-pharmacist might not know that they’re both ACE [angiotensin-converting enzyme] inhibitors, and it would be dangerous to take them together.”
Change Now or Falter Experts advise pharmacists to begin now to shift some of their focus from inpatient care to transition of care—or risk suffering financially. “My perception is the pharmacy clinician thinks it’s someone else’s responsibility to follow up on medications,” said Bonnie Kirschenbaum, MS, FASHP, a Boulder, Colo.-based, independent health care consultant specializing in reimbursement issues. “But if penalties shrink the hospital’s budgets, that means the pharmacy’s budget shrinks too.” Ms. Kirschenbaum said many pharmacists are resistant to adopting a more basic, proactive stance when it comes to interacting with patients. “Pharmacists like being an antibiotic or infectious disease specialist; they don’t like sitting with Grandma Smith going over her diabetic
see IPPS RULE, page 26
if you caused this infection, we’re going to dock you, because you’re responsible for it.’ ” Observation status: The final rule distinguishes inpatient admission from observation status—for which hospitals receive lower rates of Medicare reimbursement because it’s considered as an outpatient stay. Pharmacists can help their facilities navigate this tricky area of IPPS policy, according to Bonnie Kirschenbaum, MS, FASHP, a
Boulder, Colo.-based independent consultant. “The key is to make sure your facility is billing based on the admission status of the patient, rather than their physical location,” she stressed. “I would strongly urge that pharmacists take ownership of this important area of payment policy.” (For tips on how to make sure your hospital’s billing department is actually billing correctly, based on the admission status of patients, see this month’s
“Reimbursement Matters” column by Ms. Kirschenbaum on page 22.) Hospital VBP: The update for this program measures the quality of care patients report they received in the hospital. “It gives providers an incentive to make sure [that] we’re doing a good job educating patients, listening to what they say, and that we display a good bedside manner,” Mr. Anderson said. “Things you think would be fundamental, but sometimes don’t happen in hospitals.” —D.S.
For adult patients with iron deficiency anemia (IDA) of various etiologies Injectafer® is an iron replacement product indicated for the treatment of IDA in adult patients1
t who have intolerance to oral iron or have had unsatisfactory response to oral iron
INDICATIONS Injectafer® (ferric carboxymaltose injection) is an iron replacement product indicated for the treatment of iron deficiency anemia in adult patients who have intolerance to oral iron or have had unsatisfactory response to oral iron, and in adult patients with non-dialysis dependent chronic kidney disease. Injectafer® is contraindicated in patients with hypersensitivity to Injectafer® or any of its inactive components.
IMPORTANT SAFETY INFORMATION Serious hypersensitivity reactions, including anaphylactic-type reactions, some of which have been life-threatening and fatal, have been reported in patients receiving Injectafer®. Patients may present with shock, clinically significant hypotension, loss of consciousness, and/or collapse. Monitor patients for signs and symptoms of hypersensitivity during and after Injectafer® administration for at least 30 minutes and until clinically stable following completion of the infusion. Only administer Injectafer® when personnel and therapies are immediately available for the treatment of serious hypersensitivity reactions. In clinical trials, serious anaphylactic/anaphylactoid reactions were reported in 0.1% (2/1775) of subjects receiving Injectafer®. Other serious or severe adverse reactions potentially associated with hypersensitivity which included, but were not limited to, pruritus, rash, urticaria, wheezing, or hypotension were reported in 1.5% (26/1775) of these subjects. In clinical studies, hypertension was reported in 3.8% (67/1775) of subjects. Transient elevations in systolic blood pressure, sometimes occurring with facial flushing, dizziness, or nausea were observed in 6% (106/1775) of subjects. These elevations generally occurred immediately after dosing and resolved within 30 minutes. Monitor patients for signs and symptoms of hypertension following each Injectafer® administration. In two randomized clinical studies, a total of 1775 patients were exposed to Injectafer®, 15 mg/kg of body weight, up to a single maximum dose of 750 mg of iron on two occasions, separated by at least 7 days, up to a cumulative dose of 1500 mg of iron. Adverse reactions reported by ≥2% of Injectafer®-treated patients were nausea (7.2%); hypertension (3.8%); flushing/hot flush (3.6%); blood phosphorus decrease (2.1%); and dizziness (2.0%).
t who have non-dialysis dependent chronic kidney disease Up to 750 mg can be delivered in a single dose*1
t Give 2 doses separated by at least 7 days for a total cumulative dose of 1500 mg
t Administer intravenously by
– Infusion over at least 15 minutes – Slow push injection at the rate of approximately 100 mg (2 mL) per minute over at least 7.5 minutes * For patients weighing 50 kg (110 lb) or more, give each dose as 750 mg. For patients weighing less than 50 kg (110 lb), give each dose as 15 mg/kg body weight. †
When administered via infusion, dilute up to 750 mg of iron in no more than 250 mL of sterile 0.9% sodium chloride injection, USP, such that the concentration of the infusion is not <2 mg of iron per mL and administer over at least 15 minutes. When administering as a slow intravenous push, give at the rate of approximately 100 mg (2 mL) per minute.
NDC 0517-0650-01 For more information, please call American Regent Customer Service at 800-645-1706 or visit Injectafer.com For reimbursement assistance, please call the Reimbursement Hotline at 877-4-IV-IRON REFERENCE: 1. Injectafer® [package insert]. Shirley, NY: American Regent, Inc.; 2013.
The following serious adverse reactions have been most commonly reported from the postmarketing spontaneous reports: urticaria, dyspnea, pruritus, tachycardia, erythema, pyrexia, chest discomfort, chills, angioedema, back pain, arthralgia, and syncope.
Please see Brief Summary of the Full Prescribing Information on the following page.
Injectafer® is manufactured under license from Vifor (International) Inc., Switzerland. ©2013 American Regent, Inc. Printed in USA FCM002 Iss. 08/2013
Pharmacy Practice News â€˘ October 2013
Donâ€™t Let Distractions Lead to Revenue Loss T
hereâ€™s no question that the pharmacy management team has an overflowing basket of tasks and important issues to tackle and myriad infrastructure problems to solve. But letâ€™s not forget that ensuring a healthy revenue stream should be a priority. This monthâ€™s column will focus on some of the reimbursement areas that may have been overlooked or pushed aside. Once again, Medicare will be the model dis-
Brief Summary of Full Prescribing Information
INJECTAFERÂŽ (ferric carboxymaltose injection)
cussed as third-party payors and Medicaid often follow its lead.
A Quick Review The Centers for Medicare & Medicaid Services (CMS) uses two primary reimbursement models for hospital payments. The first, known as the Inpatient Prospective Payment System (IPPS), is based on the Diagnostic-Related Group (DRG) model and, with few exceptions,
INDICATIONS AND USAGE: InjectaferÂŽ (ferric carboxymaltose injection) is an iron replacement product indicated for the treatment of iron deďŹ ciency anemia in adult patients: s WHO HAVE INTOLERANCE TO ORAL IRON OR WHO HAVE HAD UNSATISFACTORY RESPONSE TO ORAL IRON