Second Quarter 2017Vol. I, Issue 2

P&T Update

Special Points of Interest:• P&T Update-Formulary

Addition/Deletion

• Policy and Procedures Update

• The progression of Treatment inSevere Clostridium difficile

• FDA Investigates Outbreak ofHepatitis A Illnesses Linked toRaw Scallops

• Role of Clonidine in treatingNeonatal Abstinence Syndrome

• Revised GOLD Guidelines for the Treatment of Chronic Obstructive Pulmonary Disease

• Statin therapy and the Associated Risk of Diabetes

EDITORS:Andre Emont,Pharmacy Director

Victor Pardo,Operations Manager

Michael Chu,Clinical Pharmacy Manager

Nishat Faruqui,Clinical Pharmacist

Helen Horng,Clinical Pharmacist

Gregory Eilinger,Clinical Pharmacist

Merlin Punnoose,Clinical Pharmacist

Clement Chen,Clinical PharmacistArun Mattappallil,Clinical Pharmacist

Joshua ColoradoClinical Pharmacist

Formulary AdditionsNivolumab (Opdivo®) - formulary addition – Approved• Nivolumab is a human immunoglobulin G4 (IgG4) monoclonal antibody that binds

to PD-1 receptors preventing interaction with PD-L1 and PD-L2. It’s used as a 2ndline agent for a number of oncology indications including Malignant Melanoma,Non-Small Cell Lung Cancer, Hodgkin’s Lymphoma, Renal Cell Carcinoma, andSquamous Cell Carcinoma of the Head or Neck

Polyethylene glycol 3350 (Miralax®) line extension addition – Approved• Pharmacy proposed line extension consideration for polyethylene glycol 3350

(MiraLAX®) addition. Product has been used on a non-formulary status for years.Class review of laxatives was presented. Currently, UH Formulary includes glycerinsuppositories, lactulose and polyethylene glycol-electrolyte (Golytely®) in osmoticaction class. Members support this line extension, citing in pediatric population,glycerin only acts on the colon, in certain cases, option of MiraLAX® to act in smallintestine & colon after glycerin trial is needed. Laxative class review:

Formulary DeletionsMeningococcal polysaccharide vaccine (Menomune®) deletion – Approved• Manufacturer (Sanofi Pasteur) has decided to discontinue the production of

Menomune®. Formulary deletion proposed. UH currently have Menveo® as ACIPrecommended off label alternative to Menomune® for meningococcal vaccine.

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Policies & Procedures/Floor Stock Update1. 707-500-110 High Risk High Alert/Look Alike

Sound Alike Medication Policy RevisionFollowing Medication Safety Committee reviewand approval of eliminating the RN double sign forMAR actions on lookalike sound alike andepidural/intrathecal medication, revisions are madein the policy to accurately reflect new practice ofsingle sign for the affected medications.

2. 707-700-106 Who May Administer MedicationPolicy RevisionFollowing Medication Safety Committee reviewand approval of eliminating the RN double sign forMAR actions on lookalike sound alike andepidural/intrathecal medication, revisions are madein the policy to accurately reflect new practice ofsingle sign for the affected medications.

3. 707-700-114 Epidural Anesthesia Policy RevisionFollowing Medication Safety Committee reviewand approval of eliminating the RN double sign forMAR actions on lookalike sound alike andepidural/intrathecal medication, revisions are madein the policy to accurately reflect new practice ofsingle sign for the affected medications.

4. 707-700-101 Administering & ChartingMedications to Patients Policy RevisionTwo policies both focusing on medicationadministration and charting administrations in EPICwere combined. This policy includes all aspects ofcurrent medication administration practices,including BCMA and Carpuject usage.

5. 5-Fluorouracil (5-FU) overdose/toxicity Policy –ApprovedA new Policy and Guideline for patients determinedto have a 5-FU overdose was developed andendorsed by the oncology subcommittee. Policydictates the oncologist on-call should be paged assoon as an overdose is identified, and an actionplan is outlined depending on the severity of theoverdose.

6. UH Pharmacy policy & procedure table ofcontent for 2017 approval – ApprovedList of Pharmacy Policy and Procedures werepresented for 2017 approval. Pharmacy Policiesand Procedures: 184Protocols & guidelines: 7Dangerous abbreviation ListLook alike, sound alike, high risk, high alertmedication list

7. 5-Fluorouracil (5-FU) overdose/ toxicity newpolicy – ApprovedA new Policy & Guideline for patients with 5-FUoverdose was developed by the oncologysubcommittee Policy dictates the oncologist on-callshould be paged as soon as an overdose isidentified, and an action plan is outlineddepending on the severity of the overdose.

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Since the publication of SHEA/IDSA in 2010,additional clinical trials and studies have beencarried out to strengthen the recommendation ofvancomycin as first line treatment in severe CDI,which are reflected in more recent guidelines. Thechange in recommendation with subsequentguidelines demonstrates a progression invancomycin superiority to metronidazole in severeCDI. Recently published cohort studies further buildon the existing evidence of vancomycin superiorityin treatment of severe CDI over metronidazole.

References:1. 1. Xiuzhen Di, Nan Bai, Xin Zhang, Bin Liu, Wentao Ni, Jin

Wang, Kai Wang, Beibei Liang, Youning Liu, Rui Wang. A meta-analysis of metronidazole and vancomycin for the treatment ofClostridium difficile infection, stratified by disease severity. TheBrazilian Journal of Infectious Diseases, Volume 19, Issue 4, Pages339-349.

2. Zar FA, Bakkanagari SR, Moorthi KM, Davis MB. A comparisonof vancomycin and metronidazole for the treatment ofClostridium difficile-associated diarrhea, stratified by diseaseseverity. Clin Infect Dis. 2007;45:302–307.

3. Stevens VW, Nelson RE, Schwab-Daugherty EM, Khader K,Jones MM, Brown KA, Greene T, Croft LD, Neuhauser M,Glassman P, Goetz MB, Samore MH, Rubin MA. ComparativeEffectiveness of Vancomycin and Metronidazole for thePrevention of Recurrence and Death in Patients WithClostridium difficile Infection. JAMA Intern Med.2017;177(4):546-553. doi:10.1001/jamainternmed.2016.9045.

Contributed by:Ugne Damkauskaite, PharmD Candidate Class of 2019St. John’s University College of Pharmacy and Health Sciences

The Centers for Disease Control andPrevention reported nearly half a millioninfections due to Clostridium difficileamong patients in 2016. Clostridiumdifficile infection (CDI) may be classified asmild, moderate or severe depending uponsymptoms. Any classification of CDI isrecognizably dangerous with warrantedprompt treatment, however, a majorconcern lays in treatment of severe CDI(patients with white blood cell count >15kor serum creatinine >1.5x baseline) due tothe likely possibility of fatality. The greatermortality associated with severe CDIplaces a dependence on guidelines forupdated information as they ultimatelydefine treatment for infection ofClostridium difficile [1].

To date there are five publishedguidelines for the treatment of CDI: Society forHealthcare Epidemiology of America/ InfectiousDisease Society of America (SHEA/IDSA), AmericanCollege of Gastroenterology (ACC), EuropeanSociety of Clinical Microbiology & InfectiousDiseases (ESMID), World Society of EmergencySurgery (WSES), and Australasian Society forInfectious Disease. Guidelines have been publishedover the last seven years with Australasian beingmost current. All guidelines recognizedmetronidazole or vancomycin as appropriatetreatment for CDI with vancomycin being first linefor treatment of severe CDI. SHEA/IDSA (2010) andACC (2013) provided a strong recommendation forfirst line vancomycin treatment in severe CDI, butwith moderate quality evidence as support,meaning further strong research is likely to have animpact in the recommendation. The backing ofSHEA/IDSA recommendation with moderate qualityevidence has made vancomycin initiation for severeCDI less likely [3]. On the other hand, ESMID(2014), WSES (2015), and Australasian (2016)provided a strong recommendation with highquality evidence for first line vancomycin treatmentin severe CDI. The discrepancy in informationamongst guidelines is solely attributable to thelaggard update following publication of significantstudies, which may impact or change currentrecommendations.

The progression of Treatment in Severe Clostridium difficile

Vancomycin

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FDA Investigates Outbreak of Hepatitis A Illnesses Linked to Raw Scallops

Hepatitis A is a contagious liver disease resultingfrom infection with Hepatitis A virus (HAV). Thedisease ranges in severity from mild illness that lastsa couple of weeks to severe symptoms that can lastup to several months. Hepatitis A spreads when aperson ingests fecal matter through contact withfood, drinks, or objects contaminated by feces of an

infected person. Symptoms of the disease includefatigue, abdominal pain, jaundice, abnormal livertests, dark urine, and pale stool. People at risk fordeveloping Hepatitis A are the following: pregnantwomen, young children, elderly, individuals who areimmunocompromised, have decreased stomachacidity or liver dysfunction. Therefore, people whohave underlying liver conditions or otherpreexisting conditions should be vaccinated forHAV.

In a recent finding, the FDA and CDC workedwith the Hawaii department of health (DOH) toinvestigate an outbreak of Hepatitis A linked toconsuming raw scallops.The FDA did a tracebackinvestigation where they would try to see where thescallops were sourced from. The investigationdetermined that Sea Port Products Corp importedthe scallops that were later given to sushirestaurants in Hawaii where sick people reportedeating. On August 17, 2016, the FDA did laboratoryanalysis on two scallop samples that had confirmedpositive results for Hepatitis A. The samples wereimported by Sea Port Products Corp and were made

on November 23rd, 2015. The FDA, CDC, andHawaii DOH informed Sea Port Products Corp thattheir scallops were the likely cause of the illnesses.On August 18, 2016, Sea Port Products Corpvoluntarily recalled 3 lots of frozen Bay Scallopsmade on November 23rd and 24th of 2015. The lotnumbers were 5885, 5886, and 5887. Theserecalled products were distributed originally toCalifornia, Hawaii, and Nevada. Sea Ports ProductsCorp stated that the recalled products were notintended for retail sale. The FDA worked closelywith the recall group to makes sure the recallprocess was efficient and that the products wereremoved from the market.

To combat this recent outbreak case, the FDA hasa list on selecting and serving fresh and frozen seafood safely. There are recommendations includedfor restaurants and retailers as well as for consumersin practicing seafood safety. For restaurant andretailers, they should wash and sanitize areas suchas refrigerators that store potentially contaminatedproducts. They should also wash all cutting boards,surfaces, and utensils to prevent potentialcontamination. Employees should also focus onwatching hands efficiently with warm soap andwater. Consumers should also make sure to washhands properly after using the bathroom to preventthe spread of diseases such as Hepatitis A. By takingthe appropriate steps in practicing proper hygieneand cleanliness, individuals can contribute to theefforts in preventing future outbreaks fromoccurring.

References:1. Disease Outbreak Control Division. | Hepatitis A Outbreak

2016. http://health.hawaii.gov/docd/hepatitis-a-outbreak-2016/. Published August 18, 2016.

2. FDA Investigates Outbreak of Hepatitis A Illnesses Linked toRaw Scallops. US Food & Drug Administration.https://www.fda.gov/Food/RecallsOutbreaksEmergencies/Outbreaks/ucm517289.htm#Products. Published August 24, 2016.

3. Larsen L. How Does Hepatitis A Get Into Shellfish? FoodPoisoning Bulletin.https://foodpoisoningbulletin.com/2016/how-does-hepatitis-a-get-into-shellfish/. Published March 19, 2017.

4. Outbreak of hepatitis A in Hawaii linked to raw scallops.Centers for Disease Control.

Contributed by:Kalim Ahmed, Pharm D Candidate Class of 2019Fairleigh Dickinson University

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Infants could experience withdrawal symptomsafter abrupt discontinuation of opioids which theywere exposed to. This condition is called “Neonatalabstinence syndrome” (NAS). The major symptomsof this condition are irritability, hypertonia, failureto gain weight, poor sucking reflex, autonomicinstability. According to Tolia et al3, the admissionrate for NAS has increased from 2004 to 2009. Lowsocioeconomic status and education level andgenetic predisposition are some of the factors thatmay explain the increasing incidence of NAS inhospital. There are effective treatments for opioidoverdose such as Methadone; however its use maybe one of the reasons that NAS is increasing.

Clonidine is an interesting drug for treating NAS.The NAS affects multiple body systems by changingthe balance of neurotransmitter (such as serotonin,noradrenaline, dopamine, acetylcholine,corticotropin) levels. There are two modes oftreatment for NAS; Nonpharmacological andPharmacological. According to American academyof Pediatrics (AAP) opioids are the first-line agentsfor treating NAS. One of the new and safepharmacological approaches is to treat withClonidine. This drug worksby stimulating the alpha2-autoreceptors in the brainand resulting in decreasingsympathetic outflow causedby over-excited mureceptors.Clonidine is eliminated bykidney and its clearancedepends on the renalfunction of the child. It clearsat a slower rate as the childmatures. It has a good safetyprofile and its effect on Bloodpressure has been shown tobe clinically insignificant andit doesn’t have cardiovascularside effects. Clonidine is agood alternative to othertherapies such asPhenobarbital. It doesn’tcause respiratory depressionas phenobarbital. It is mostcommonly formulated asoral. Clonidine is also used as

an adjuvant agent for treating and shortening thetreatment duration of NAS. According to Broome2,“A target plasma concentration of 0.8-1.0 ng/mLwas confirmed by previous studies to provideadequate sedation in pediatric patients ages 1-11years”. If after reaching the target concentrationthe patient is still experiencing NAS symptoms, analternative agent should be used rather thanincreasing the dose. Additional clinical studies arerequired to optimize the dosing strategy.

References:1. Streetz N. Vonya, Gildon L. Brooke, Thompson F. Dennis, “Role

of Clonidine in Neonatal Abstinence Syndrome: A SystematicReview”, 2016. Vol.50(4) 301-310. Sage Journal.

2. Broome Laura, So Tsz-Yin, “Neonatal Abstinence Syndrome:The use of Clonidine as a Treatment Option”.

3. Tolia VN, Patrick SW, Bennett MM, et al. Increasing incidenceof the neonatal abstinence syndrome in U.S. neonatal ICUs. NEngl J Med. 2015;372:2118-2126. doi:10.1056/NEJMsa1500439.

Contributed by:Siavash Mojibian, PharmD Candidate, Class of 2019, Rutgers University

Role of Clonidine in Treating Neonatal Abstinence Syndrome

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Chronic Obstructive Pulmonary Disease (COPD) is acommon, preventable and treatable diseasecharacterized by persistent respiratorysymptoms and airflow limitation. Theselimitations are due to airway and/oralveolar abnormalities caused bysignificant exposure to noxiousparticles such as cigarette smoke.COPD is currently the thirdleading cause of death in theUnited States and the fourthleading cause of death globally.The revised Global Initiative forChronic Obstructive LungDisease (GOLD) guidelines werepublished in February to furtherimprove the quality of COPDunderstanding and treatment.

The revised GOLD guidelines statethat a confirmed diagnosis of COPDrequires the ratio FEV1/FVC < 0.7 to indicatepersistent airflow limitations. FEV1 is used to assess theseverity of airflow limitation and classifies patients asGOLD 1 (mild) to 4 (severe). It is also necessary toassess the severity of symptoms by using the ModifiedBritish Medical Research Council (mMRC)questionnaire for breathlessness or the COPDAssessment Test (CAT) which gives a comprehensiveassessment of symptoms such as cough, chesttightness, and sputum production. Symptoms andexacerbation history are used to classify patients intogroups A-D. Groups are used to determinepharmacological treatment.

Treatment recommendations for an acute COPDexacerbation include the use of short acting beta2-agonists with or without short-acting anticholinergics,systemic corticosteroids for a duration of 5-7 days, andwhen indicated, antibiotics may also be used for 5-7days. The use of systemic corticosteroids andantibiotics are shown to reduce the duration ofrecovery/hospitalization. Methylxanthines are notrecommended for exacerbations as they require neartoxic doses to be effective. Non-invasive ventilation(NIV) is recommended over invasive ventilation for thetreatment of acute respiratory failure in hospitalizedpatients because it has been shown to decreasemorbidity and mortality.

Cigarette smoking is one of the main risk factors forCOPD. Smoking cessation has become a primary goal

for patients at risk for COPD. Since COPD ispreventable and treatable, but not curable,

prevention of disease progression isessential. In addition, the updatedguidelines recommend thatpatients with COPD receive theinfluenza and pneumococcalvaccines to prevent lowerrespiratory tract infections. It isrecommended that patients bescreened for alpha-1 antitrypsindeficiency because although it isnot common, it plays a role inCOPD and patients may benefit

from augmentation therapy.Although treatment options

continue to improve, prevention andearly treatment remain the top priorities

in reducing the prevalence of COPD and therisk of exacerbations.

References:1. Bernhard N, Lepper PM, Vogelmeier C, et al. Deterioration of

quality of life is associated with the exacerbation frequency inindividuals with alpha-1-antitrypsin deficiency – analysis fromthe German Registry. International Journal of ChronicObstructive Pulmonary Disease. 2017;12:1427-1437.doi:10.2147/COPD.S130925.

2. Global Initiative for Chronic Obstructive Lung Disease (GOLD).GOLD 2017 global strategy for the diagnosis, management,and prevention of chronic obstructive pulmonary disease,2017 report. Accessed June 1, 2017.

3. Joachim H. Ficker, Klaus F. Rabe, Tobias Welte, Role of dualbronchodilators in COPD: A review of the current evidence forindacaterol/glycopyrronium, Pulmonary Pharmacology &Therapeutics, Volume 45, August 2017, Pages 19-33, ISSN1094-5539, https://doi.org/10.1016/j.pupt.2017.04.002.

4. Marcos PJ, Nieto-Codesido I, de Jorge Dominguez-Pazos S,Huerta A, Marquez E, Maiso A, Verdeal R, Otero-Gonzalez I,Blanco-Aparicio M, Montero-Martinez C.Treatment WithSystemic Steroids in Severe Chronic Obstructive PulmonaryDisease Exacerbations: Use of Short Regimens in RoutineClinical Practice and Their Impact on Hospital Stay. ArchBronconeumol. 2017 Apr 28. pii: S0300-2896(17)30078-9.doi: 10.1016/j.arbres.2017.03.012.

5. Sadatsafavi M, Sin DD, Zafari Z, et al. The Association BetweenRate and Severity of Exacerbations in Chronic ObstructivePulmonary Disease: An Application of a Joint Frailty-LogisticModel. American Journal of Epidemiology. 2016;184 (9):681-689. doi:10.1093/aje/kww085.

Contributed by:Gianna Galioto, PharmD Candidate Class of 2019St. John's University College of Pharmacy and Health Sciences

Revised GOLD Guidelines for the Treatment of ChronicObstructive Pulmonary Disease

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P. Smith, M.D., M.S., and deputy director of theDivision of Metabolism and Endocrinology at theU.S. Food and Drug Administration (FDA), clarifiedthat the importance of statin therapy. He states,“The benefits of statins in reducing heart attacksand strokes should generally outweigh this smallincreased risk.”4

Current data may suggest that diabetes is acaution for statin therapy. However, data from themetaanalysis conducted by Sattar et. al., illustratesthat 255 subjects over 4 years will cause one newcase of diabetes. The authors from this meta-analysis and the FDA deputy director advised thatclinical practice should not be changed based onthese findings as the benefits of statin therapyoutweigh the associated risk.

References:1. Sagonowsky E. “California Lipitor plaintiffs win a chance to

argue the Pfizer medication triggered their diabetes.”FiercePharma. http://www.fiercepharma.com/legal/judge-sends-pfizer-lipitor-cases-to-ca-state-courts. Published May 25,2017.

2. Lipitor [package insert]. New York, NY: Pfizer; 2015.3. Sattar N, Preiss D, Murray HM, et al. : “Statins and risk of

incident diabetes: a collaborative meta-analysis of randomisedstatin trials.” Lancet.2010;375(9716):735–42. 10.1016/S0140-6736(09)61965-6

4. U.S. Food & Drug Administration. “Consumer Update:Controlling Cholesterol with Statins.” https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm293330.htm. PublishedFebruary 29, 2012.

Contributed by:Nitin Kumar, PharmD & MBA Candidate, Class of 2019Fairleigh Dickinson University – School of Pharmacy and HealthSciences

On May 25, 2017, a California U.S. District Judgeupheld a ruling that will allow a group of women tolitigate their claim that Pfizer’s statin loweringmedication, Lipitor, caused in their diabetes. Theblock-buster medication once brought in $9.58billion in global sales for Pfizer in 2011 and thosesales have since diminished to $1.7 billion aroundthe world last year.1 The pharmaceutical giant isnow defending against these claims in court.

In the Stroke Prevention by Aggressive Reductionin Cholesterol Levels (SPARCL) trial, with 4731patients, 2365 patients were treated with Lipitor80mg pharmacotherapy and 2366 patients weregiven a placebo for a approximately 4.9 years. Inthis trial, “diabetes was reported as an adverseevent in 144 subjects (6.1%) in the atorvastatingroup and 89 subjects (3.8%) in the placebogroup.”2

In a comparative meta-analysis conducted bySattar et. al., published in the Lancet in February2010, 13 statin random clinical trials were reviewed.The results from the meta-analysis illustrated thatstatin therapy was associated with a “9% increase inthe incidence of diabetes (odds ratio [OR] 1.09;95% CI 1.02-1.17), with little heterogeneity(I(2)=11%).”3 This risk was observed to be thegreatest in the older population.

In a consumer update published on February 16,2017, the FDA acknowledged the claim that theone of the major risks that patient’s on statintherapy should be cautious about are an increasedrisk of developing type 2 diabetes. However, James

Statin Therapy and the Associated Risk of Diabetes

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Welcome New Pharmacists

Merit HenenDr. Merit Henen received her Doctor of Pharmacy degree from Long Island

University in Brooklyn, New York in 2013. She worked in a retail pharmacyboth during school and after graduation, before deciding to change her areaof practice to diversify her experience. She pursued a staff pharmacistposition at University Hospital to expand her knowledge of pharmacy, alwaystrying to learn new things. During her free time she enjoys going out withfriends, spending time with her family, and traveling.

Peter IbrahimPeter Ibrahim, graduated Mansoura pharmacy school - Egypt 2011.

He is joining uhnj with great passion . He Always wants to take care ofour patients. Clinical researching is his reason that encourages him tojoin our team at uhnj. Looking forward to escalate and develop hisclinical skills at UHNJ.

Srujal Patel, Pharm.D., BCPS.Dr. Srujal Patel earned her Doctor of Pharmacy degree from

Long Island University School of Pharmacy in Brooklyn in 2007.During her clinical rotations, she explored a variety of careerswithin pharmacy. After graduation, she worked at long term carepharmacy and at an independent community pharmacy. She gother board certification in pharmacotherapy specialist in 2015 toadvance her career. She is excited to work at the UniversityHospital. This opportunity will fulfill her dream to advance hercareer and to provide better patient care. She enjoys spendingtime with her family, traveling, cooking, running and swimming.

Jason M. Donnelly, Pharm D.Dr. Jason Donnelly earned his Doctor of Pharmacy degree from

the Massachusetts College of Pharmacy and Allied HealthSciences (MCPHS) in Boston, in 2010. After graduating, Jasonworked in retail pharmacy for seven years as the PharmacyManager in multiple locations before being hired by UniversityHospital. In his free time, Jason enjoys spending time with hisfamily, playing golf and watching a variety of sports.