PHARMACY AND THERAPEUTICS UPDATESODIUM BICARBONATE INTERCHANGE TO SODIUM ACETATEDue to the sodium bicarbonate shortage, St. Dominic’s has been employing a one-to-one switch from sodium bicarbonate to sodium acetate. We will continue to reserve sodium bicarbonate for cardiac arrest situations (sodium bicarbonate syringes will continue to be stocked on code carts but par levels will be reduced) and extemporaneous compounding for cardioplegia solutions. Outside of these indications sodium bicarbonate will be automatically changed to the equivalent sodium acetate dose. Incidentally, use of sodium acetate also has a cost advantage versus use of sodium bicarbonate.

ORAL ADMINISTRATION OF IM METHYLERGOVONINE SOLUTIONMethylergonovine is an uterotonic agent commonly deployed adjunctively to oxytocin for the management of post-partum hemorrhage. Th e oral methylergovonine tablet form has been sold to Lupin Pharmaceuticals, and there has now been a signifi cant price increase to over $50 per tablet. An automatic therapeutic interchange will be implemented whereby the oral tablet formulation will be switched to an equivalent dose of the IM formulation given via oral route. Th e extent of absorption of the tablet, based upon plasma concentrations, was found to be equivalent to that of the IM solution given orally.

CALCIUM CHLORIDE INTERCHANGE TO CALCIUM GLUCONATE Due to the IV calcium chloride shortage, St. Dominic’s has been employing an automatic interchange of calcium chloride to calcium gluconate (one gram of calcium chloride is equivalent to three grams of calcium gluconate) for indications of electrolyte replacement, serum calcium restoration during CRRT, and acute hyperkalemia. Calcium chloride will continue to be stocked in code carts while supplies last for use in cardiac arrest and peri-arrest scenarios. Th ere is a cost advantage to using calcium gluconate as well.

Pharmacy Pulse2017 • VOLUME 2

FORMULARY CHANGESNON-INSULIN DIABETES MEDICATIONSAll oral and non-insulin injectable diabetes medications, including metformin, will be removed from the inpatient hospital formulary. Management of inpatient hyperglycemia for both diabetics and non-diabetics will be performed with insulin products only. Reasons for this proposal include best-practice recommendations for using only insulin in an acute care setting, diffi culty of titration of oral doses, and adverse eff ects and complications of oral agents, such as heart failure, hypoglycemia, drug interactions, lactic acidosis, and acute kidney injury. Th is formulary restriction was approved by P&T in concert with support from the St. Dominic Hospitalist group and Medical Executive Committee. Th e full formulary removal will be implemented with Cerner go-live and until that time, the pharmacotherapists will be monitoring patients on these medications while educating providers on the upcoming formulary change and assisting them with transitions to insulin-only regimens.

RANITIDINE ORAL SOLUTION/SYRUPRanitidine oral solution was removed from formulary due to lack of utilization and increased cost compared to other formulary alternatives, such as oral or intravenous famotidine.

VELTASSA® (PATIROMER)Veltassa® (patiromer) was added to the formulary for use in hyperkalemia. Veltassa® has better potassium binding capacity compared to Kayexalate® and may provide similar benefi ts for hyperkalemia without causing laxation, theoretically decreasing nursing and environmental services workload, as well as providing improved infection control. It will be added to the hyperkalemia protocol as an option for patients with potassium greater than or equal to 5.5 mEq/L as a one-time dose ± daily doses “as needed” for potassium greater than or equal to 5.5 mEq/L. Kayexalate® will stay on formulary as an option for rectal administration since most prescribers are more familiar with its use at this point in time.

DRUG SHORTAGES: A PHARMACY PERSPECTIVEBY JOSHUA STOKES, PHARMD In hospitals and clinics all across the country, the unfortunate reality of drug shortages plagues health care professionals on a daily basis. The Great Shortage of 2017 has become a multi-drug fiasco that includes sodium bicarbonate, calcium gluconate, calcium chloride, and dextrose 50 percent. Other drugs on shortage are unavailable as ready-to-use injectable formula-tions, such as labetalol and Bicillin-LA syringes. There are other drugs that have been only sporadically available, such as promethazine for intravenous injection and 8.5 percent amino acid solution used in dialysis.

To call a few of these items “drugs” is somewhat laughable. Even the New York Times reported this month on the great irony of the sodium bicarb shortage: “It is unavailable to hospitals but can be found in almost every kitchen cabinet.” The fact that dextrose and baking soda are bringing the healthcare industry to its knees seems like the plot of a dark comedy film, but this is the world we live in. It is perplexing and unnerving that in 2017 America, the economy that serves as the world’s engine cannot seem to produce a solution that prevents this from happening. In 2013, the FDA decided to take action. It released a 40-page plan on mitigating and pre-venting drug shortages. Isn’t that a relief? One would hope there would be an upcoming addenda to that plan that will let the world know when the salary dollars behind drafting it will start to show a return on investment.

While prescribers have the constant headache of figuring out alternate ther-apies for drugs in short supply, there is a task just as daunting for the phar-macy department in each hospital. How do we effectively communicate shortages and adapt to their constraints so that our patients can still receive life-saving medications? The problem set for pharmacy is multi-faceted:

1) Not all shortages are telegraphed. Some drugs that are about to go on shortage show signs of it a week or more beforehand. However, the events can also play out like this: one day, the drug is available from distributors, and the next day, there is none available. We don’t always get a heads-up from manufacturers or distributors when there are problems. Depending on how much drug the hospital has on hand, that can create a frantic situ-ation. At a moment’s notice, the pharmacy has to be prepared to effectively communicate a shortage to the medical staff, suggest and analyze the avail-ability of alternatives and then adapt to the product we receive – whatever that is.

2) Shortages create exponentially higher work load on pharmacy. The pharmacy department is sometimes forced to buy products that are in bulk form and then transform them into something usable by the nursing staff. Drug sometimes has to be diluted to a different concentration, and almost always, it has to be drawn into unit dose form by hand, dose by dose. In the process, beyond-use dating for these medications take a beating, with some only able to have a 24-hour expiration date. This ensures that more will be needed the following day. The point of this is not a woe-is-pharmacy rant. The point is to make known what very few are aware of what is taking place

FDA SAFETY ALERT CORNERThis is a summary of the recent FDA Drug Safety Alert Communications. Outlined below are alerts, FDA recommendations and St. Dominic specific actions to address the FDA Recommendations for each safety alert. Please see individual safety alert documents for detailed alert information at http://www.fda.gov/Safety/MedWatch/SafetyInformation/default.htm

PIOGLITAZONE LINKED TO INCREASED RISK OF BLADDER CANCERAlert: Updated FDA review concludes that use of type 2 diabetes medicine pioglitazone may be linked to an increased risk of bladder cancerSummary: As a result of an updated review, FDA has concluded that use of the type 2 diabetes medicine pioglitazone (Actos, Actoplus Met, Actoplus Met XR, Duetact, Oseni) may be linked to an increased risk of bladder cancer. The labels of pioglitazone-containing medicines already contain warnings about this risk, and we have now approved label updates to describe the additional studies we reviewed. Public was alerted about the possible risk of bladder cancer in September 2010 and June 2011 based on interim results from a 10-year epidemiologic study. FDA changed the labels of pioglitazone-containing medicines in August 2011 to include warnings about this risk, and required the manufacturer to modify and continue the 10-year study.FDA Recommendation Healthcare Professionals should not use pioglitazone in patients with active bladder cancer, and should carefully consider the benefits and risks before using pioglitazone in patients with a history of bladder cancer. Patients should contact their health care professionals if they experience any of the following signs or symptoms after starting pioglitazone, as these may be due to bladder cancer:•Blood or a red color in the urine•New or worsening urge to urinate

behind the scenes. The pharmacy is having to unit dose prep seven or eight different high-use medications that normally can be purchased in ready-to-use form. Of course, there is no emergency drug shortage personnel line item in the budget.

3) We got a shipment, so does that mean the shortage is resolved? Not exactly. Unfortunately, medications on shortage will often be made avail-able for a brief time and again fall off the grid. When the pharmacy buyer notices that Drug X, which has been unavailable for months, is now avail-able, what is the natural reaction? Buy all they will let me have! The only problem is this reaction is shared by every other buyer in the country, so what seemed like a resolution to the shortage only becomes a new shortage due to stockpiling. Not knowing when a shortage is truly resolved can be taxing on the pharmacy department. Making a premature announcement that a shortage is over will cause big problems and compromise trust in the department, but at the same time, nobody wants to hold out and sit on product when it can be used. The conundrum is a weekly experience.

The institution of St. Dominic’s has been affected by drug shortages in a big way. The pharmacy department has managed things to the best of its ability, and one thing should be known by others in the organization: we are work-ing hard to do our part in finding a way through the recent problems. We are constantly meeting and brainstorming outside-the-box ideas for man-aging these crises. Simply staying on top of the information and crafting a plan for shortages is literally a full time job. Yet we make it work, one way or another.

•Pain when urinating.St. Dominic’s Actions: Continue current therapeutic monitoring as outlined in the Pharmacy Department Drug Therapy Monitoring Policy..

VIBERZI (ELUXADOLINE) AND SE-RIOUS PANCREATITIS IN PATIENT WITHOUT A GALLBLADDER Alert: FDA warns about increased risk of serious pancreatitis with irritable bowel drug Viberzi (eluxadoline) in patients without a gallbladder Summary: : The U.S. Food and Drug Administration (FDA) is warning that Viberzi (eluxadoline), a medicine used to treat irritable bowel syndrome with diarrhea (IBS-D), should not be used in patients who do not have a gallbladder. An FDA review found these patients have an increased risk of developing serious pancreatitis that could result in hospitalization or death. Pancreatitis may be caused by spasm of a certain digestive system muscle in the small intestine. As a result, we are working with the Viberzi manufacturer, Allergan, to address these safety concerns.From May 2015, when Viberzi was first approved, through February 2017, FDA received 120 reports of serious cases of pancreatitis or death.* Among the 68 patients who reported their gallbladder status, 56 of them did not have a gallbladder and received the currently recommended dosage of Viberzi. Seventy-six patients were hospitalized, of which two patients died. These two patients did not have a gallbladder. Some cases of serious pancreatitis or death also reported sphincter of Oddi spasm (n=6) or abdomen pain (n=16) (see Data Summary).FDA Recommendation: Health care professionals should not prescribe Viberzi in patients who do not have a gallbladder and should consider alternative treatment options in these patients. Hospitalizations and deaths due to pancreatitis have been reported with Viberzi use in patients who do

not have a gallbladder. Symptoms of pancreatitis have occurred with just one or two doses of Viberzi at the recommended dosage for patients who do not have a gallbladder (75 mg), and who do not consume alcohol.Physicians can consider both over-the-counter (OTC) or FDA-approved prescription medicines to treat symptoms associated with IBS-D such as OTC bismuth subsalicylate (Kaopectate and Pepto-Bismol), OTC loperamide (Imodium), and prescription medicine diphenoxylate/ atropine (Lomotil) for diarrhea. Also consider OTC medicines for gas relief such as simethicone (Gas-X, Mylicon). Other FDA-approved prescription medicines for IBS-D include alosetron hydrochloride (Lotronex) and the antibiotic rifaximin (Xifaxan).St. Dominic’s Actions: Share alert with St. Dominic Hospital G.I. nurse practitioners. Th is is a non-formulary item at St. Dominic. Continue current therapeutic monitoring as outlined in the Pharmacy Department Drug Th erapy Monitoring Policy.

SERIOUS ALLERGIC REACTIONS WITH CHLORHEXIDINE GLUCONATEAlert: FDA warns about rare but serious allergic reactions with the skin antiseptic chlorhexidine gluconate Summary: Th e U.S. Food and Drug Administration (FDA) is warning that rare but serious allergic reactions have been reported with the widely used skin antiseptic products containing chlorhexidine gluconate. Although rare, the number of reports of serious allergic reactions to these products has increased over the last several years. As a result, we are requesting the manufacturers of over-the-counter (OTC) antiseptic products containing chlorhexidine gluconate to add a warning about this risk to the Drug Facts labels. Prescription chlorhexidine gluconate mouthwashes and oral chips used for gum disease already contain a

IS OUR CAP HAT TOO LARGE?BY CASSIE CREW, PHARMD Recently, the Hospital Acquired Pneumonia (HAP)/Ventilator Associated Pneumonia (VAP) guidelines from the Infectious Disease Society of Amer-ica (IDSA) were updated in 2016. Among the most notable updates was the removal of the diagnostic entity “Healthcare Associated Pneumonia (HCAP),” which has traditionally been used to identify patients who may need additional antibiotic coverage for multidrug resistant (MDR) patho-gens, such as methicillin-resistant staphylococcus aureus (MRSA), when they present with pneumonia from the community. Rather than focusing on healthcare exposure, the IDSA instead recommended considering more patient-centered risk factors when selecting candidates for empiric MDR pathogen coverage. Unfortunately, recent literature has demonstrated that empiric MRSA coverage is vastly over-prescribed. Th e incidence of MRSA in community acquired pneumonia is anywhere from 0.7 percent to 2.5 percent, yet vancomycin coverage is empirically deployed in up to 30 per-cent of cases 1, 2, 3. Andrew Shorr created a scoring system to help identify patients that were considered low, medium, or high risk for community acquired pneumonia caused by MRSA. In both the development set as well as the validation set of patients (about 6,000 patients total), those identi-fi ed as “low risk” had an MRSA positivity rate of less than a 10 percent, giving this scoring system a negative predictive value nearing 90 percent. We sought to evaluate whether this scoring system could be used to better identify patients with community acquired pneumonia who were at low risk for MRSA, thus avoiding unnecessary empiric antimicrobial coverage.

Goal: Determine if using a stratifi ed risk factor scoring system has appropriate negative predictive value to assist in ruling out patients who would not benefi t from empiric MRSA coverage

Methods: Retrospective chart review from June 2015 to December 2015 which included any patient diagnosed with pneumonia that was prescribed vancomycin therapy. Th ere were 158 patients that were initially screened and 100 that met inclusion criteria. Patients were excluded if their diagnosis was healthcare associated, aspiration, or hospital acquired pneumonias.

Primary Outcome: Determine the prognostic performance of the Shorr score; more specifi cally the negative predictive value of this scoring system.

Baseline characteristics are included below, of note, 15 percent of patients were admitted to the intensive care unit.

warning about the possibility of serious allergic reactions in their labels.FDA Recommendation: Health care professionals should always ask patients if they have ever had an allergic reaction to any antiseptic before recommending or prescribing a chlorhexidine gluconate product. Advise patients to seek immediate medical attention if they experience any symptoms of an allergic reaction when using the products. Consider using alternative antiseptics such as povidone-iodine, alcohols, benzalkonium chloride, benzethonium chloride, or parachlorometaxylenol (PCMX) when any previous allergy to chlorhexidine gluconate is documented or suspected.St. Dominic’s Actions: Identifying, updating, and verifying allergies are part of the normal workfl ow for patient care services and pharmacy services. Chlorhexidine is an available as an allergy choice if needed to be added to a patient profi le. Share alert with Infection Control Committee. Continue current therapeutic monitoring as outlined in the Pharmacy Department Drug Th erapy Monitoring Policy.

Th e scoring system used was slightly diff erent than the original Shorr score: any patient with diabetes was allotted a point for that characteristic and intravenous antibiotic use was extended from “in the past 30 days” to “in the past 90 days.” Th e occurrence of each characteristic of the scoring system is listed below, along with the points given per characteristic.

Results: Blood culture results were available for the entire sample with no positive MRSA results. In addition, other culture data available for this sample included: 34 percent nares PCR results and 32 percent induced sputum results. Over half of the patients in the sample had a low score classifi cation and had received at least one dose of vancomycin. A positive MRSA culture was not found in any of the available culture data of the low risk population in our sample, accruing a negative predictive value of 100 percent. Th e medium risk group had only one positive nares PCR culture. If the low and medium risk groups were considered to be “non-high” and those groups were classifi ed together to avoid empiric MRSA coverage, this would yield a negative predictive value of 99 percent.

Conclusion: If this scoring system had been employed upon admission for this sample of patients, a 52 percent reduction in vancomycin use would have resulted. Extrapolating that cost reduction over a 12 month period, St. Dominic Hospital could save approximately $28,000 USD per year. Although there are still many questions to be answered regarding the medium and high risk patient populations, the adjusted Shorr score’s validity held true in our low risk patient population. Th is scoring system could be used as an additional tool for pharmacists and prescribers when deciding on empiric antibiotic regimens for community acquire pneumonia.Questions: If you have any further questions/comments or would like more information on this research project, please feel free to contact ccrew@stdom.com. Co- investigators: Wesly Pierce, PharmD and John Cleary, PharmD References1. Self WH, Wunderink RG, Williams DJ, Zhu Y, Anderson EJ, Balk RA, Fakhran SS,Chappell JD, Casimir G, Courtney DM, Trabue C, Waterer GW, Bramley A, Magill S,Jain S, Edwards KM, Grijalva CG. Staphylococcus aureus Community-acquired Pneumonia: Prevalence, Clinical Characteristics, and Outcomes. Clin Infect Dis.2016 Aug 1;63(3):300-9. doi: 10.1093/cid/ciw300. Epub 2016 May 8.2. Moran GJ, Krishnadasan A, Gorwitz RJ, Fosheim GE, Albrecht V, Limbago B, TalanDA; EMERGEncy ID NET Study Group. Prevalence of methicillin-resistantstaphylococcus aureus as an etiology of community-acquired pneumonia. Clin InfectDis. 2012 Apr;54(8):1126-33.3. Prina E, Ranzani OT, Polverino E, Cillóniz C, Ferrer M, Fernandez L, Puig dela Bellacasa J, Menéndez R, Mensa J, Torres A. Risk factors associated with potentially antibiotic-resistant pathogens in community-acquired pneumonia. Ann Am Th orac Soc. 2015 Feb;12(2):153-60.4. Shorr AF, Myers DE, Huang DB, Nathanson BH, Emons MF, Kollef MH. A risk score for identifying methicillin-resistant Staphylococcus aureus in patients presenting to the hospital with pneumonia. BMC Infect Dis. 2013 Jun 6;13:268.

IMPACT OF A PHARMACY CONSULT SERVICE ON GLYCEMIC MANAGEMENTBY SOOMIN KIM, PHARMDDiabetes is a growing problem in the US with 29.1 million diagnosed with diabetes mellitus and 86 million who are considered pre-diabetic. We strive to achieve glycemic control in the inpatient setting because a variety of diff erent patient populations (COPD, cardiac surgery, abdominal surgery, stroke) 3, 4, 5, 6 have been found to be adversely aff ected by uncontrolled glucose. In the inpatient setting, ADA guidelines recommend a goal BG (blood glucose) of 140-180 mg/dL in both critical and non-critical care patients and that treatment be reviewed and changed to prevent further hypoglycemia when BG <70 mg/dL. Despite uncontrolled blood glucose leading to adverse patient outcomes, one study found that in patients who were hyperglycemic in >30 percent of their readings, 65 percent had no change in their insulin order during the fi rst fi ve days of hospitalization. Something that we have established at our institution in hopes of achieving better glycemic control is the Diabetes Care Service. Th is service allows physicians to consult pharmacy for glycemic management, and under this protocol pharmacists can initate and adjust glycemic therapy. We wanted to determine how the pharmacy department was performing in glycemic management and if more hospitals would benefi t from implementing such a service.

Goal: To determine how the pharmacy-based glycemic consult service at St. Dominic Hospital compares to usual care regarding glycemic control and complications of hyperglycemia

Methods: Th is study was an observational retrospective chart review from November 2016 – March 2017 including patients admitted to the hospitalist service and patients who were consulted for the Diabetes Care Service, both with ≥2 blood glucose values outside 70-180 mg/dL within a period of one day. Patients had to have 3-5 blood glucose results per day on days for which data was collected. Patients were excluded if they had DKA at any point during admission, if they were admitted to the ICU, or if their length of stay too short to assess for the primary outcome.

Primary outcome: Time to the second out-of-range BG value (<70 mg/dL or >180 mg/dL) aft er 48 hours allowed for glycemic correction

Secondary outcomes: Mortality and nosocomial infection

Baseline characteristics: Demographic characteristics were similar between the two groups, except for more African American patients in the Diabetes Service Care group and more Caucasian patients in the usual care group. Th ere was a slightly higher A1c in the usual care group, and a notably higher number of patients in the Diabetes Service Care group who had a diabetes related admission diagnosis.

Results: For the primary outcome of time to secobd out of range blood glucose aft er the allotted amount of time for correction, we found there was no signifi cant diff erence, with the usual care group at 65 hours and Diabetes Service Care group at 62 hours (P=0.362). Of note, with our outcome, the shorter the time, the worse controlled were the blood glucoses. Th ere were also a higher percentage of patients in the Diabetes Care Group admitted for diabetes-related diagnosis’s, the overall risk of hyperglycemia may have been higher for this group. For the secondary outcomes, there were four patients in the Diabetes Care Service group who experienced a nosocomial infection compared to one in the usual care group. Th ere was one mortality in each group.

Discussion/Conclusion: Strengths of the study include that we had similar results as a previous study that evaluat-ed the impact of a pharmacy-based consult service on glycemic control compared to usual care, in that there was no signifi cant diff erence between the two groups. Additionally, this is a unique service that is not off ered in many hospitals around the nation, and it adds valuable insight to the current lack of available literature. Lastly, the study measured how long glycemic control was achieved for aft er given a specifi c amount of time. Th is provides a bigger picture than taking an average glucose value at one specifi c point in time. Weaknesses of the study include that it was a retrospective, cohort study. Th e sample size was small, and we did not end up meeting power. However, with a p-value of 0.36, it is unlikely that results would have been signifi cantly diff erent even if we had met power. Th ere may have been some sampling bias in that patients selected to be in the Diabetes Care Service group were consulted to pharmacy by only a few internists so it does not provide the whole picture, as pharmacy is consulted for most patients in the ICU. Another sampling bias could have come from comparing the Diabetes Care Service to the hos-pitalist service. Glycemic management is one of the areas of focus for hospitalists. Because there was no signifi cant diff erence between the Diabetes Care Group and the hospitalist group, this speaks to glycemic control capabilities of pharmacists and could potentially justify an expanded role for pharmacy in glycemic management. Lastly, 48 hours may not have been enough time for correction, which is why we may have not seen a signifi cant diff erence. Future studies may extend the interval to 72 hours or longer to see a signifi cant diff erence.

Co- Investigators: Bill Burford, RPh and John Cleary, PharmD

References1. Centers for Disease Control and Prevention. National Diabetes Statistics Report, 2014. http://www.cdc.gov/diabetes/data/statistics/2014StatisticsReport.html. 2. American Diabetes Association. Standards of Care in Diabetes 2017. http://professional.diabetes.org/sites/professional.diabetes.org/fi les/media/dc_40_s1_fi nal.pdf.3. Baker EH, Janaway CH, Philips BJ, et al. Hyperglycemia is associated with poor outcomes inpatients admitted to hospital with acute exacerbations of chronic obstructive pulmonary disease. Th orax. 2006;61(4):284–289.4. McAlister FA, Majumdar SR, Blitz S, Rowe BH, Romney J, Marrie TJ. Th e relation between hyperglycemia and outcomes in 2,471 patients admitted to the hospital with community-acquired pneumonia. Diabetes Care. 2005;28(4):810–815.5. Capes SE, Hunt D, Malmberg K, Pathak P, Gerstein HC. Stress hyperglycemia and prognosis of stroke in nondiabetic and diabetic patients: a systematic overview. Stroke 2001;32:2426-32.6. Pomposelli JJ, Baxter JK 3rd, Babineau TJ, Pomfret EA, Driscoll DF, Forse RA, Bistrian BR. Early postoperative glucose control predicts nosocomial infection rate in diabetic patients. JPEN J Parenter Enteral Nutr. 19987. Schnipper JL, Barsky EE, Shaykevich S, Fitzmaurice G, Pendergrass ML. Inpatient management of diabetes and hyperglycemia among general medicine patients at a large teaching hospital. J Hosp Med. 2006 May;1(3):145-50.8. Efi rd LE, Golden SH, Visram K, Shermock K. Impact of a pharmacy-based glucose management program on glycemic control in an inpatient general medicine population. Hosp Pract (1995). 2014 Feb;42(1):101-8.

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or email: jdana@stdom.com