The role of lead pharmacist provides a pathway to leadership.

For almost a decade, the profession of pharmacy has been discussing and planning for a potential shortage in leadership. In 2005, the American Journal of Health-System Pharmacy published a survey summary assessing the current and future supply of candidates for leadership roles in pharmacy, defined as pharmacy directors and middle managers. Of the survey population, only 30% of current practitioners were interested in pursuing a leadership position in the future. The concerns regarding future leadership were raised in light of a projected vacancy of more than 70% of current leadership roles. Recruitment was singled out as one of the most challenging aspects of identifying future leaders. One recommendation of the report was that current practitioners pursue alternative leadership opportunities.

	One method that could be utilized to fill a potential gap in leadership is the implementation of a lead pharmacist role. The introduction of lead pharmacists is a single solution that can address multiple needs. In addition to serving as a way to identify and develop future leaders, the implementation of lead pharmacists can provide an immediate benefit to an organization. In coordination with their manager, the lead pharmacist can serve as an extension of their respective manager or assistant director, depending on the organization structure, thereby allowing for greater depth of influence and knowledge of a practice area. Additionally, these roles allow for more formal leadership training to occur in a supervised manner and can be a method of succession planning.

The department of pharmacy at the University of North Carolina Hospitals (UNCH) is one hospital that has implemented the lead pharmacist role. The current model of lead pharmacists at UNCH initiated from a requirement by the North Carolina Board of Pharmacy. The design and implementation of the position in the outpatient retail pharmacy setting produced benefits for the management structure within these areas and provided growth opportunities for staff. After this initial success, lead pharmacist positions were implemented in inpatient areas, both operational and clinical.

Ideally, the individual has practiced as a clinician or in an operational role prior to transitioning into a lead position and is typically informally recognized by colleagues as a leader. Extensive knowledge of an area of practice is vital to the success of a lead pharmacist position. Understanding the details of workflow and common issues encountered by the staff are valuable assets that can lead to 

many health systems continue to expand as does the scope of many leadership positions. As a result, managers often find it challenging to maintain a consistent presence in their operational areas. Lead pharmacists can provide a more consistent day-to-day presence within the specific work 

area and, as a result, can often troubleshoot issues in real time. Some organizations have seen expansion of pharmacy services into nontraditional practice sites or new facilities outside of the main organization. These areas may not be large enough to warrant an entire management structure but can be the perfect opportunity for appointing a lead pharmacist to serve as the site contact and lead day-to-day operations in an area. Additionally, the rapid growth 

and change within health care requires extensive planning. Lead pharmacists can provide managers with additional time for planning functions and operational insights necessary for appropriate plans.

The specific duties and responsibilities of a lead pharmacist position should vary between practice settings and provide flexibility for the manager to align the position to fit their specific needs. Potential responsibilities or duties include:

Day-to-day availability in the practice area

Vision planning/operational planning with manager

Providing assistance with operational tasks

Coordinating or tracking progress of ongoing projects and 

Initially, many of these roles will require the manager to invest time in training the lead pharmacist. Staff members also will need time to adjust to having a new leader involved in issue resolution and decision-making. For instance, the lead pharmacist and manager must focus on the development of trust in each other’s ability to determine which issues require intervention by a manager and which issues can be resolved by the lead pharmacist. Simultaneously, success is dependent upon the staff becoming comfortable with answers provided by the lead pharmacist and not the manager.

Human resources tasks can be some of the most time-consuming functions a manager is required to complete. Engaging a lead pharmacist in some of these roles can produce significant relief for the manager. For example, the lead pharmacist can conduct interviews for new staff, including candidate screening. Once the new staff member is on-site, the lead pharmacist can become an excellent point of contact for onboarding and training during the orientation period. The lead pharmacist could also assist with professional development plans, corrective action, and annual performance evaluations.

For all the potential benefits a lead pharmacist role can provide, it is not without its challenges. Involving staff members early as the position is developed and seeking their feedback regarding the selection can help promote support for the position. There is potential for flexibility in the design of these positions, with the most common being a continuation of clinical or operational practice with a minimum commitment of time for lead responsibilities. Dedicating time for new tasks and responsibilities will result in a need for coverage in the practice setting from other pharmacists.

The selection method will be organization-specific as some could require that a lead pharmacist be processed as an entirely new position while other organizations could consider it simply a change in a working title. Depending upon organizational policies, these positions may be permanent position changes or term-based appointments (eg, 12 months). Engagement with the human resources and compensation departments early in the process will ensure a more smooth transition for the position and that any change is in line with organizational policies.

Once the title and process have been arranged with human resources, engaging staff in the process of designing position responsibilities and selecting their leaders is an important step that can help affirm support for the position. Whenever possible, employees should be able to participate in the process. At minimum, their feedback should be solicited by the manager or a formal interview could be conducted for the selection.

After a lead pharmacist is selected, he or she will often need to undergo some form of leadership development training. Utilization of a departmental or organizational training program is an ideal place to start. National pharmacy organizations also have a variety of leadership training resources available, often at little or no cost. During the onboarding process it also will be important to outline specific responsibilities and establish a regular meeting time. It can take time to establish position responsibilities and for the candidate to develop proficiency. Often the new responsibilities can overlap with the manager’s former or current responsibilities. It is essential that this overlap is noted and discussed. Failure to specify responsibilities can result in significant frustration and incomplete tasks.

From this point forward, the manager and the lead pharmacist should do much of the vision planning and goal setting as a partnership. It will be important that the lead pharmacist is aware of the plans and vision so he or she can support and reinforce these with the rest of the staff.

Throughout this entire process, a significant amount of patience is necessary from all parties. Commitment to developing the team, including the new leader, must be modeled by the manager. The staff may need time to adjust to the new process and to having a new leader in the group. They will have to develop trust in the decision-making process. The manager must reinforce the role of the lead pharmacist and support their decisions. It is helpful if the manager and new leader establish a regular dialogue to review specific scenarios and potential solutions and debrief after decisions are made by the new leader.

The establishment of a lead pharmacist position can be a mutually beneficial endeavor for both the manager and the staff as a whole. Career advancement opportunities and professional development are long-term outcomes of a well-designed lead pharmacist position. Current leadership benefits greatly from additional leadership support and greater insight into the needs and expectations of the frontline staff. Lead pharmacist position descriptions must be designed with both the needs of the team and the manager in mind, and the leader selected should be able to meet both. Involvement and feedback from staff will help to ensure a smooth transition and a successful position in the long term.

Articles

Viewpoints

Leadership and Growth Opportunities for Clinical Pharmacists

Clozapine is an atypical antipsychotic for the treatment of schizophrenia.

Thought disorders such as schizophrenia are marked by 1 or more of the following symptoms: delusions, hallucinations, disorganized thinking, grossly disorganized or abnormal motor behaviors, and negative symptoms (disruptions to normal behavior) (see Figure).

Clozapine, the first atypical antipsychotic available, is widely accepted to be superior to other antipsychotics, not only for treating positive symptoms, but also for treat- ing negative symptoms.

 Generally, a shortcoming of antipsychotics is their inability to treat negative symptoms, which are frequently cited as the principal culprit in preventing improved social and occupational outcomes. Clozapine is FDA approved for treatment-resistant schizophrenia and reduction in the risk of recurrent suicidal behavior in schizophrenia or schizoaffective disorder.

Clozapine was first synthesized in 1960 and was used in clinical studies in the early 1970s. However, it was removed from the market in the United States in 1974 after 14 cases of agranulocytosis were reported in Finland, 8 of which resulted in death.

Because of its superiority over other antipsychotics (also known as neuroleptics), clozapine was reintroduced to the American market in 1990, with specific monitoring parameters. 

Clozapine monitoring was one of the first formal Risk Evaluation and Mitigation Strategy programs. It is required that the patient, physician, and pharmacy be registered with a clozapine manufacturer registry and report white blood counts (WBC) and absolute neutrophil counts (ANC) weekly during the first 6 months of therapy, every 2 weeks during the second 6 months of therapy, and monthly after 1 year of therapy. Currently, clozapine is available in the United States from 4 manufacturers (see Table). All of these companies have online registries, making it unnecessary to fax hard copies of lab results to the manufacturer or report results by telephone. 

Because of the monitoring requirements and risk of agranulocytosis, clozapine is not a first-line agent for the treatment of schizophrenia. Generally, a patient must fail or be intolerant to at least 2 other antipsychotics before a trial of clozapine is warranted. 

In addition to agranulocytosis, there are other adverse effects clinicians must consider. Seizures are dose related and generally are not seen in patients taking less than 600 mg daily. For patients who are on more than 600 mg daily, prophylactic antiepileptic therapy is recommen- ded, preferably with divalproex. Concomitant carbamazapine use is contraindicated due to the cumulative risk of bone marrow suppression.

Myocarditis is a temporally related, potentially fatal side effect that has gained more recognition in the last decade. Clozapine-induced myocarditis is an immunoglobulin E—mediated allergic response that can develop during the first 8 weeks of treatment. Its true incidence is unknown, but has been reported as high as 1% to 2%.

Some countries require mandatory reporting of myocarditis signs and symptoms during the first 6 months of treatment. At minimum, it is prudent to empirically check cardiac enzymes, brain natriuretic peptide, eryrthrocyte sedimentation rate, and/ or C-reactive protein at baseline and weekly for the first 4 to 8 weeks with the complete blood count with differential. Any symptoms such as elevated heart rate, temperature, or chest pain/discomfort should be investigated. If myocarditis is diagnosed, the clozapine must be stopped immediately and the patient provided with supportive care. If caught early enough, clozapine-induced myocarditis is reversible. It generally is not recommended that the patient be rechallenged with clozapine if myocarditis develops.

Small bowel obstruction is another rare side effect, but it can be fatal. Because clozapine is so highly anticholinergic and patients on clozapine are, by nature, poor historians, severe constipation leading to small bowel obstruction is a real risk. All patients on clozapine should be provided with a bowel regimen such as docusate 100 mg orally twice daily at minimum. Polyethylene glycol, both as a standing order and as needed, may be used as an alternative or in addition to a stool softener.

All patients started on clozapine will have some degree of orthostatic hypotension initially during dose titration. Up to 20% of patients will have tachycardia. Both of these results are related to the drug’s highly anticholinergic properties and its alpha receptor affinities. Symptomatic treatment is recommended (eg, increasing fluid intake, rising slowly from seated or prone position). Beta-blockers may be used if the heart rate exceeds 120 beats per minute or the patient is uncomfortable.

Finally, as with any atypical anti-psychotic, metabolic syndrome may develop with long-term clozapine use. Clozapine is generally regarded as the worst metabolic offender among anti-psychotics; however, this high risk is often outweighed by the immeasurable benefit of improved quality of life that many patients experience when starting clozapine. Additionally, patients who were quite sedentary prior to clozapine initiation may be able to fully participate in a diet and exercise program after some symptom resolution. While the utility is still debatable, occasionally metformin will be added on to an atypical antipsychotic such as clozapine to help mitigate the metabolic effects.

When reviewing a clozapine order or prescription, several questions should be answered to ensure safe and appropriate prescribing. Is the patient adherent to clozapine? If so, their home dose may be continued safely. If adherence is uncertain, restarting the home dose at full strength may result in cardiovascular collapse due to severe orthostatic hypotension.

Until adherence is confirmed, it’s best to start at 25 mg daily or, at minimum, one-half of the home dose. 

Ensure that the patient has had a complete blood count with differential in the last week and that WBC and ANC counts are greater than 3500/ mm

, respectively. The pharmacist will need to report these laboratory values to the appropriate registry and may assist in registering the physician. An extra step to ensure safety would be to obtain myocarditis laboratory values if the patient has been started on clozapine within the last 8 weeks. 

As mentioned earlier, ensuring that a bowel regimen is available is important for patient comfort. A review of the medication list to identify duplicate therapeutic indications is also warranted. For example, patients taking clozapine would never require benztropine, as clozapine has inherent anticholinergic properties. Added benztropine only increases side effects such as cognitive dulling, dry mouth, and constipation.

																									Finally, pharmacists may assist in transitions of care by ensuring that the patient has the appropriate laboratory values required upon discharge and that the outpatient pharmacy of choice stocks clozapine. A quick telephone call to the outpatient pharmacy can assist with a smooth transition from inpatient to outpatient. 

Lindsey Hedgepeth Kennedy, PharmD, BCPS, BCPP, is a clinical specialist in psychiatry at University of North Carolina Hospitals department of pharmacy.

Clinical Care Focus

Clozapine: A Primer For Pharmacists

It’s that time of year again: the runny nose, sore throat, muscle aches, fatigue, chills, and fever of the 2014-2015 influenza season will soon be in full swing. Although these symptoms may seem benign, the influenza virus has the potential to cause devastating infections. The first, and hopefully final, pandemic of the 21st century occurred during the 2009-2010 influenza season. It is estimated that between 151,700 and 575,400 people worldwide succumbed to the 2009 H1N1 virus during its first year of circulation. Unlike previous pandemics, the 2009 H1N1 virus was fatal in a significant proportion of non-elderly patients. Approximately 80% of H1N1 deaths occurred in people younger than 50 years.

 However, 2009’s H1N1 was nowhere near as deadly as the influenza pandemic of 1918. The “Spanish Flu,” as it was known, exceeded the death toll of World War I, killing an estimated 50 million people.

 Thankfully, increased immunization rates and advancements in epidemiologic forecasting make these catastrophic influenza outbreaks less and less likely, but this progress has not eliminated the virus’ impact on health care.

Influenza is a member of the orthomyxovirus family and comprises 3 basic types: A, B, and C. The virus can be further delineated into subtypes dependent on the glycoprotein surface antigens hemagglutinin (H) and neuraminidase (N). Nomenclature of influenza viruses is described in the following order: virus type, geographic site of origin, strain number, year of isolation, and virus subtype. For instance, one strain of influenza could be described as A/ California/07/2009 (H1N1). Pandemics usually occur when the genetic material of 2 or more of strains combine and create a different combination of surface antigens. This genetic exchange is referred to as an antigenic shift.

 In 1957, an antigenic shift involving a change in viral glycoproteins from H1N1 to H2N2 resulted in a pandemic that caused roughly 70,000 deaths.

Assessing the past 31 influenza seasons, the Centers for Disease Control and Prevention (CDC) found that approximately 80% of influenza infections occurred between January and March. However, the 2 most recent influenza seasons, 2012-2013 and 2013- 2014, were considered outliers in that the peak of these seasons occurred much earlier. While the timing was unusual, most of the viruses identified during these seasons were similar to the familiar vaccine-targeted strains. The predominant circulating influenza subtype of the 2013-2014 season was H1N1. Unlike the aforementioned pandemic of 2009, the 2013-2014 season’s H1N1 affected mostly elderly patients.

During the 2012-2013 season, the CDC estimated that flu vaccination prevented 79,000 hospitalizations in the United States.

 While the constantly changing nature of the influenza virus makes predictions of virulence and activity difficult, vaccination remains the best method of influenza prevention.

Vaccine recommendations for the 2014-2015 influenza season were announced in late August by the CDC Advisory Committee on Immunization Practices. The CDC continues to recommend annual influenza vaccinations for patients 6 months and older. The trivalent and quadrivalent formulations are available and contain the same virus strains as last season. Both formulations include the A/California/7/2009 (H1N1), A/Texas/50/2012 (H3N2), and B/Massachusetts/2/2012-like viruses. The quadrivalent formulations incorporate an additional strain, the B/ Brisbane/60/2008-like virus.

 No additional guidance or preference in formulations is provided regarding the 2should be used with caution, and the decision should be carefully assessed by the patient’s health care provider. Contraindications to the LAIV can be found in Online Table 2. Those who are not eligible for receipt of the LAIV should be directed to a provider capable of obtaining and administering the inactivated influenza vaccine (IIV) unless the patient has a history of anaphylaxis with previous influenza vaccines.

Table 2: Contraindications to the Live-attenuated Influenza Vaccine (LAIV)

				-        Age < 2 years or >49 years of age

				-        Age 2 through 4 years in patients who have asthma or who have had a wheezing episode in past 12 months

				-        Antiviral medication use in previous 48 hours

New Aspects of the 2014-2015 Recommendations

The primary change to the recommendations for this year relates to the use of the live-attenuated influenza vaccine (LAIV) in children. It is now recommended that intranasal LAIV be administered in children 2 to 8 years of age, as studies demonstrate its increased protection against influenza. It is important to note that the CDC strongly advises against deferring vaccine administration if LAIV is unavailable. Simply put, any vaccine is better than no vaccine. Children 6 months to 8 years of age still require 2 doses of influenza vaccine, given at least 4 weeks apart, if they did not receive at least 2 doses of the seasonal influenza vaccine and at least 1 dose of the pandemic 2009 (H1N1) vaccine previously. LAIV contraindications have also become less stringent when it comes to patients with chronic comorbidities. Instead of strictly advocating against the use of LAIV in these patients, the CDC suggests that LAIV should be used with caution, and the decision should be carefully assessed by the patient’s health care provider. Contraindications to the LAIV can be found in Online Table 2. Those who are not eligible for receipt of the LAIV should be directed to a provider capable of obtaining and administering the inactivated influenza vaccine (IIV) unless the patient has a history of anaphylaxis with previous influenza vaccines.

Strong efforts should be made to ensure immunization in individuals who are at high risk of developing influenzarelated complications. High-risk persons include children younger than 5 years, adults 65 years or older, pregnant women, and patients with certain chronic comorbidities or weakened immune systems (eg, cardiovascular disease, diabetes, HIV/AIDS, malignancy). Since no vaccines are available for infants younger than 6 months, the only source of influenza antibodies available for these patients is their mother. Consequently, vaccination is strongly recommended for pregnant women, but the LAIV should not be administered (see Online Table 2).

High-dose influenza vaccines are available for patients over the age of 64 years. With 4 times the amount of antigen, these vaccines have been shown to provide a stronger immune response. High-dose influenza vaccine was modestly more effective for the prevention of influenza compared with standard dose in a recently published trial that included almost 32,000 adults 65 years and older. Laboratory-confirmed influenza occurred in 1.4% of patients in the high-dose group compared with 1.9% of patients in the standard-dose group (relative efficacy of 24% [95% CI 9.7 - 36.5)]).

 While serious adverse events in this particular study appeared to be uncommon, a previous study comparing the immunogenicity of high-dose versus standard-dose influenza vaccine in patients 65 years and older found that mild and moderate local reactions occurred more frequently in patients receiving the high-dose vaccine. 14 Currently, the CDC recommends annual influenza vaccination for all patients 65 years and older, but does not provide a preference of high-dose over standard-dose influenza vaccine.

Recommendations for Patients with Egg Allergies

Another important consideration when choosing the appropriate vaccine is how it was manufactured. Certain allergens are present at various levels in the available vaccine products. The amount of egg protein (ovalbumin) is of particular concern for individuals with egg allergies. There are currently 3 different methods to create influenza vaccines: (1) egg-based, (2) cell-based, and (3) recombinant. The egg-based manufacturing process is the most commonly used method to produce live and inactivated influenza vaccines. Influenza viruses are harbored in fertilized hen’s eggs for several days to allow adequate viral replication. Subsequently, the virus undergoes several other processes, including inactivation (if necessary), purification, and testing. The amount of egg protein can be identified by its ovalbumin content (see Table1

Cell-based manufacturing follows a process similar to that of eggbased manufacturing, but instead of replicating the influenza virus in fertilized eggs, the viruses are cultured in mammalian cells. Usually a very minuscule amount of ovalbumin is found in cell-based influenza vaccines. To date, there is only 1 influenza vaccine that utilizes cell-based manufacturing: Flucelvax.

The third method relies on recombinant DNA technology to produce a 100% egg-free vaccine product. The H protein from the influenza virus is extracted and mixed with other portions of another virus. This combination is then grown in insect cells for viral replication. Flublok is the first trivalent influenza vaccine made with recombinant DNA technology.

 It was approved by the FDA in January 2013 for persons 18 through 49 years of age. Guidance in vaccine selection for patients with an egg allergy is provided by the CDC. Those who are able to consume a lightly cooked egg without experiencing a reaction can receive usual vaccinations, but should be observed for a minimum of 30 minutes after vaccination. Flublok can be administered to patients who experience hives after eating eggs or egg-containing foods, as well as patients who experience more severe reactions after egg consumption including cardiovascular, respiratory, or gastrointestinal symptoms, and patients who have required epinephrine and/or emergency medical attention after egg consumption.

Pharmacist Role in Influenza Immunization

Pharmacists are able to act at the forefront and play an integral role as advocates for influenza prevention. Because of this, it is important for pharmacists to stay up-to-date regarding influenza vaccine recommendations and vaccine availability. Regardless of the health care setting, pharmacists are able to provide helpful patient education concerning the importance of the influenza vaccine and potential complications associated with acute viral illness. At each clinical encounter, pharmacists should assess the need for the influenza vaccine and identify patients at risk for developing influenza-related complications. In the hospital setting, pharmacists can take advantage of opportunities to vaccinate patients prior to discharge. Those who are able to provide vaccinations in outpatient settings are also in a great position to promote influenza immunizations. During the 2013-2014 influenza season, the second-most common place for adults to receive their influenza vaccines was a store or pharmacy.

 With the rapidly increasing role of pharmacists in immunization and the rising popularity of walk-in outpatient/ ambulatory vaccination, the opportunity for the pharmacist to influence patient immunization rates cannot be overstated. It is important to remember that every patient interaction is a chance to prevent influenza and related complications.

Jacqueline Isip, PharmD, is a PGY-2 infectious diseases pharmacy resident at UNC Health Care. She earned her doctor of pharmacy degree at the University of Michigan.

1.     Centers for Disease Control and Prevention. First global estimates of 2009 H1N1  pandemic mortality released by CDC-led collaboration. www.cdc.gov/flu/spotlights/pandemic-global-estimates.htm. Accessed September 3, 2014.

2.     Centers for Disease Control and Prevention. CDC estimates of 2009 H1N1 influenza cases, hospitalizations and deaths in the United States. www.cdc.gov/h1n1flu/estimates_2009_h1n1.htm. Accessed February 1, 2014.

3.     US Department of Health and Human Services. Pandemic flu history. www.flu.gov/pandemic/history/.Accessed September 3, 2014.

4.     Dolin R. Influenza. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson J, Loscalzo J, eds. 

Harrison's Principles of Internal Medicine. 

18th ed. Columbus, Ohio: McGraw-Hill Education; 2011. Accessed September 13, 2014. http://accesspharmacy.mhmedical.com/content.aspx?bookid=331&Sectionid=40726944.

5.     Centers for Disease Control and Prevention. Atkinson W, Wolfe S, Hamborsky J, eds. 

Epidemiology and Prevention of Vaccine-Preventable Diseases.

 12th ed, 2nd printing. Washington, DC: Public Health Foundation; 2012.

6.     Flu Activity & Surveillance. Centers for Disease Control and Prevention website. www.cdc.gov/flu/weekly/fluactivitysurv.htm. Accessed September 1, 2014.

7.     Are you ready for flu? CDC’s recommendations and communication plans for the 2014-2015 influenza season [webinar]. www.vicnetwork.org/2014/08/14/are-you-ready-for-flu-cdcs-recommendations-and-communication-plans-for-the-2014-2015-influenza-season/. Accessed September 3, 2014.

8.     Centers for Disease Control and Prevention. Estimated influenza illnesses and hospitalizations averted by influenza vaccination — United States, 2012-13 influenza season. 

9.     Tinoco JC, Pavia-Ruz N, Cruz-Valdez A, et al. Immunogenicity, reactogenicity, and safety of inactivated quadrivalent influenza vaccine candidate versus inactivated trivalent influenza vaccine in healthy adults ≥18 years: a phase III, randomized trial. 

10.  Grohskopf LA, Olsen SJ, Sokolow LZ, et al. Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices — United States, 2014-15 influenza season. 

11. Centers for Disease Control and Prevention Advisory Committee on Immunization Practices. Update on influenza vaccine safety monitoring. Presented at the Advisory Committee on Immunization Practices meeting, June 2013, Atlanta, Ga. www.cdc.gov/vaccines/acip/meetings/meetings-info.html.

12.  Centers for Disease Control and Prevention. Live attenuated influenza vaccine [LAIV] (the nasal spray flu vaccine). www.cdc.gov/flu/about/qa/nasalspray.htm. Accessed September 13, 2014.

13. DiazGranados CA, Dunning AJ, Kimmel M, et al. Efficacy of high-dose versus standard-dose influenza vaccine in older adults. 

14. Falsey AR, Treanor JJ, Tornieporth N, Capellan J, Gorse GJ. Randomized, double-blind controlled phase 3 trial comparing the immunogenicity of high-dose and standard-dose influenza vaccine in adults 65 years of age and older. 

15.  Flucelvax [package insert]. Cambridge, MA: Novartis; March 2014.

16.  Flublok [package insert]. Meriden, CT: Protein Sciences Corp; March 2014.

17.  Des Roches A, Paradis L, Gagnon R, et al. Egg-allergic patients can be safely vaccinated against influenza. 

18.  Centers for Disease Control and Prevention. Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP) — United States, 2011. 

19.  Centers for Disease Control and Prevention. National early season flu vaccination coverage, United States, November 2013. www.cdc.gov/flu/fluvaxview/nifs-estimates-nov2013.htm. Accessed September 3, 2014.

20.  Fluzone [package insert]. Swiftwater, PA: Sanofi Pasteur; June 2014.

21.  Fluzone High-Dose [package insert]. Swiftwater, PA: Sanofi Pasteur; June 2014.

22.  Fluzone Intradermal [package insert]. Swiftwater, PA: Sanofi Pasteur; June 2014.

23.  Fluzone Quadrivalent [package insert]. Swiftwater, PA: Sanofi Pasteur; June 2014.

24.  FluLaval [package insert]. Quebec City, QC, Canada: ID Biomedical Corporation of Quebec; May 2014.

25.  FluLaval Quadrivalent [package insert]. Quebec City, QC, Canada: ID Biomedical Corporation of Quebec; May 2014.

26.  Afluria [package insert]. Parkville, Victoria, Australia: bioCSL; August 2014.

27.  Fluvirin [package insert]. Speke, Liverpool, UK: Novartis; February 2014.

28.  Flumist [package insert]. Gaithersburg, MD: MedImmune; July 2014.

29.  Fluarix [package insert]. Dresden, Germany: GlaxoSmithKline; 2014.

30.  Fluarix Quadrivalent [package insert]. Dresden, Germany: GlaxoSmithKline; 2014

31.  Centers for Disease Control and Prevention. Table: Influenza vaccines — United States, 2014-15 influenza season. www.cdc.gov/flu/protect/vaccine/vaccines.htm. Accessed on September 3, 2014.

Chronic Care Focus

Influenza Vaccines: An Overview for the 2014-2015 Season

On August 6, 2014, the FDA announced approval of Orbactiv (oritavancin) injection for treatment of acute bacterial skin and skin structure infections (ABSSSIs) caused by species of 

, including methicillin-resistant strains of 

Orbactiv does not carry any black box warnings, although use of Orbactiv is contraindicated in patients with a history of hypersensitivity reactions to the active ingredient or any excipients in the formulation. In addition, use of intravenous (IV) unfractionated heparin sodium solution is contraindicated in patients who have received Orbactiv within the previous 48 hours because Orbactiv may affect the accuracy of activated partial thromboplastin time readings. Orbactiv treatment may also falsely elevate international normalized ratio readings for up to 24 hours after use.

Orbactiv exerts concentrationdependent bactericidal activity by disrupting bacterial cell wall integrity through inhibition of polymerization and cross-linking of cell wall components known as peptidoglycans. Interfering with cell wall integrity ultimately leads to bacterial death.

In 297 patients receiving a single dose of Orbactiv, the average elimination half-life was 245 hours. Orbactiv was extensively distributed in tissues, with an average volume of distribution of 87.6 liters. Dosage adjustment is not necessary in patients with mild to moderate hepatic impairment or mild to moderate renal impairment. Studies in patients with severe hepatic impairment or severe renal impairment have not been conducted.

Each carton of Orbactiv contains a total of three 50-mL glass vials, each of which contains 400 mg of the active ingredient in a lyophilized powder for reconstitution. Before preparation, vials should be kept at room temperature. Once the IV solution is prepared, each 1200-mg dose in 1000 mL of 5% dextrose in sterile water should be infused over a period of at least 3 hours. The reconstituted solution may be kept at room temperature for up to 6 hours or may be kept under refrigeration for up to 12 hours. Importantly, this time includes the 3-hour infusion time.

During preparation, Orbactiv should only be diluted in an infusion containing 5% dextrose in sterile water, and should never be diluted in normal saline. Dilution of Orbactiv in normal saline may lead to precipitation of the drug.

Scientists evaluated the safety and efficacy of Orbactiv through 2 randomized, double-blind, multicenter, noninferiority trials. In each trial, patients with an ABSSSI received either 1 gram or 15 mg/ kg of vancomycin every 12 hours for 7 to 10 days or a single dose of Orbactiv 1200 mg infused over 3 hours. Patients with suspected gram-negative bacterial infections received aztreonam, and patients with suspected anaerobic bacterial infections received metronidazole. 

Clinical response was defined as (1) no expansion of or a reduction in the ABSSSI lesion area, (2) no fever, and (3) no use of rescue antibacterial drugs within 48 to 72 hours of receiving treatment. In trial 1, among patients who were assessed 48 to 72 hours after initiating therapy, clinical response occurred in 82.3% of patients receiving Orbactiv versus 78.9% of patients receiving vancomycin. In trial 2, at the 48- to 72-hour assessment time point, clinical response occurred in 80.1% of patients receiving Orbactiv versus 82.9% of patients receiving vancomycin. In terms of clinical response, no statistically significant differences between treatments were detected.

Orbactiv is a Pregnancy Category C medication. Levels of narrow therapeutic index medications may be affected by Orbactiv due to its weak inhibitory effects on CYP2C9 and CYP2C19, and weak induction of CYP3A4 and CYP2D6.

Orbactiv may increase the risk of bleeding when coadministered with warfarin, and may interfere with the reliability of coagulation parameter readings. Patients with previous allergies to glycopeptide antibacterial medications such as vancomycin or telavancin should be monitored carefully due to the possibility of cross sensitivity.

—associated diarrhea. In clinical trials, osteomyelitis was more common among patients receiving Orbactiv than among patients receiving vancomycin. Patients receiving Orbactiv should be monitored for signs of osteomyelitis.

Headache, nausea, vomiting, limb and subcutaneous abscesses, and diarrhea were the adverse events most commonly associated with use of Orbactiv. Each of these adverse events occurred in at least 3% of patients receiving Orbactiv in clinical studies. For a complete discussion of potential adverse events and drug interactions with Orbactiv, please consult the product package insert.

Michael R. Page, PharmD, RPh, earned his doctor of pharmacy degree at the Ernest Mario School of Pharmacy at Rutgers, The State University of New Jersey.

		FDA approves Orbactiv to treat skin infections [press release]. FDA website. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm408475.htm. Accessed October 2014.

		Orbactiv (oritavancin) [package insert]. Parsippany, NJ: The Medicines Company; 2014.

Formulary Drug Review

Orbactiv by The Medicines Company

There has been much consternation over the past few years about the rising costs of medications. Examples include the exorbitant costs of newly approved medications for niche disease states, the high prices of biologics that are used by many patients for common disease states, the increased product costs due to supply chain restrictions imposed by manufacturers, and the recently recognized growth in the cost of single-source generics. It is not uncommon to find a treatment course of oral or intravenous therapy to be greater than $100,000 per year.

In response to these rising costs, health systems have attempted to capitalize on the increased revenues that can come from dispensing these medications to outpatients. The hope is that this will lead to enhanced net revenues for these nonprofits, helping to cover other areas that are not adding to the contribution margin of the organization. Historically, hospital pharmacists have focused on the acute care side of the business, but with the current focus on transitional care and prevention of readmissions, hospitals merging to become part of a health system, and the need to become a revenue center and not just a cost center, hospital pharmacies are growing their presence in the ambulatory care setting by either adding retail pharmacies and mail order or by contracting with a retail provider to offer these services.

While most people are concerned with the rising costs of medications, I decided to see if there is a silver lining here for the profession of pharmacy. While I am not advocating for expensive medications, I do believe they can provide opportunities for pharmacists. Here are 3 benefits for the profession that are created by high-cost drugs:

(1) Increased importance of clinical decision support

—Pharmacy informatics is a burgeoning area of importance for each hospital pharmacy. Finding people who are trained in and passionate about this discipline is essential to managing expensive medications, because starting a patient on the wrong therapy can be costly. The best way to ensure that the most cost-effective medication is chosen is to have more robust clinical decision support systems in use. The ones utilized currently are rudimentary at best, and without dedicated resources to develop, monitor, and optimize these alerts and triggers, information systems will not be able to take advantage of their impact. As organizations depend on these systems to drive therapy choices in the future, hopefully they can be refined so that pharmacy departments can ensure that all therapy is optimal for the patient.

(2) Increased potential for disruptive innovation

—When the preferred option is very costly, the opportunity for innovation is large. Introducing a product that is at least as good, but much less expensive, can shift a market quickly. There becomes less incentive to pay more when the cheaper option is just as good. While there are significant barriers to entry for a new medication, the continued pursuit of less expensive options drives researchers as the burden of disease continues. The opportunity for less expensive providers also is a solution. As the profession seeks provider status, the reputation of pharmacists as medication experts provides great leverage in our quest. Ensuring that all patients are on the most cost-effective therapy can provide significant cost savings to our health care system. This doesn’t mean that no patient should ever be placed on high-cost drugs, but that they should be reserved for the patients who have no better options.

—Since medications comprise an increasing portion of overall hospital costs, the pharmacy department gains importance. Pharmacy directors are held much more accountable for the department’s finances and have to explain any negative budget variance to hospital executives. The ability to reduce the cost of medications without affecting the quality of care is needed now more than ever. Because the directors of pharmacy cannot effect all of this change directly, they have to rely upon their frontline staff to intercede at the point of decision-making. Having welltrained, credentialed pharmacists positioned across the enterprise in a practice model that allows for this engagement will provide a platform to demonstrate the benefit of pharmacists in managing drug expense.

While it will take a lot of hard work and perseverance, the department of pharmacy can add value to the current health care system by improving the utilization of cost-effective medications.

Stephen F. Eckel, PharmD, MHA, BCPS, FASHP, FAPhA, FCCP, is associate director of pharmacy, University of North Carolina Hospitals, and clinical associate professor and director of graduate studies at the University of North Carolina Eshelman School of Pharmacy.

November 2014

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