Second Quarter 2012Vol. IX, Issue 2

Pharmacy and Therapeutics (P&T) UpdateFormulary Addition/Deletion

Special Points of Interest:

• P&T Update-Formulary Addition/Deletion

• Policy and Procedures Update

• Hospital Formulary Additions and DeletionsJanuary 2010—April 2012

• 2nd Quarter 2012 Employee of the Quarter

EDITORS:Andre EmontPharmacy Director

Victor PardoOperations Manager

Michael Chu Clinical Pharmacy Manager

Nishat FaruquiClinical Pharmacist

Helen HorngClinical Pharmacist

Polly JenClinical Pharmacist

Anti-Infective Subcommittee

Vaccines and immunoglobulins formulary reviewA formulary review of available vaccines and immunizations was reviewed anddiscussed. Members of the subcommittee recommended making the followingformulary changes:

Formulary deletion of DT (diphtheria, tetanus toxoid) vaccineFormulary deletion of tetanus toxoid vaccineFormulary deletion of Rabavert® rabies vaccineFormulary addition of Imovax® rabies vaccineAutomatic interchange of DT vaccine to Td vaccineAutomatic interchange to tetanus toxoid vaccine to Td vaccine

Rabies vaccines (Imovax®) – line extension – approved

The formulary addition of Imovax® rabies vaccines and the formulary deletion ofRabAvert® rabies vaccine were requested by the Anti-Infective Subcommittee. Use ofImovax® is more cost effective than RabAvert® ($183.10 vs. $200.54 per dose), andthe preparation of Imovax® is preferable.

Rabies vaccine (RabAvert®) – formulary deletion – approved

DT (diphtheria, tetanus toxoid) vaccine – formulary deletion – approved

The formulary deletion of the DT (diphtheria, tetanus toxoid) vaccine was requestedby the Anti-Infective Subcommittee based on low usage.

Tetanus toxoid vaccine – formulary deletion – approved

Formulary deletion of acyclovir (Zovirax®) topical ointment – approvedThe Anti-Infective Subcommittee recommended formulary deletion of acyclovir(Zovirax®) topical ointment given its high cost and availability of oral antiviral therapy.

Formulary deletion of oral ganciclovir – approvedOral ganciclovir has not been available due to a long term nationwide backorder.Valganciclovir is a formulary item and has a greater bioavailability than ganciclovir.

Daptomycin standard administration method – approvedThe proposal to change the standard daptomycin administration from a 30-minuteinfusion to a 2-minute injection was presented to front-line nursing staff at theDecember 2011 Patient Care Advisory Council meeting. The nursing staff did notexpress any concerns with administering daptomycin as a 2-minute injection andassured adherence to the 2-minute injection period.

Hyaluronidase human injection (Hylenex®) – line extension – approvedAmphadase® (hyaluronidase bovine injection) 150 units /mL is no longer available inthe market.A proposal was made to substitute Amphadase® with Hylenex® (hyaluronidase humaninjection) 150 units/mL for use in neonatal extravasation cases.

Hyaluronidase bovine injection (Amphadase®) – formulary deletion-approvedAmphadase® (hyaluronidase bovine injection) 150 unit /mL is no longer available in themarket. (Continued on page 2)

2

Collagenase clostridium histolyticum (Xiaflex®) –formulary addition was not deemed necessary at thistime. Collagenase clostridium histolyticum (Xiaflex®) isan enzymatic product FDA approved for themanagement of Dupuytren’s contracture. It is the firstnon-surgical treatment option for this indication.Placebo-controlled and open-label studies havedemonstrated the safety and effectiveness ofcollagenase clostridium histolyticum for themanagement of Dupuytren’s contracture. Themedication costs $3,250 per dose; a full course oftherapy can cost up to $9,750 (max of 3 dosesallowed).

Policies & Procedures Update707-500-122 Automatic therapeutic exchange policy – revision

Revisions to the automatic therapeutic exchange policywere presented for member review and approval. Thechanges reflect formulary changes recommended bythe Anti-Infective Subcommittee. Additions to thetherapeutic interchange medication list include:• Substitution of DT vaccine to Td vaccine• Substitution of RabAvert® to Imovax® rabies vaccines

• Substitution of Boostrix® to Adacel® vaccine (Tdap,tetanus toxoid, reduced diphtheria toxoid, andacellular pertussis)

• Substitution of tetanus toxoid vaccine to Td vaccine

IV Infusion update: Nitroglycerin, DOPamine andDOBUTamineNitroglycerin: for telemetry unit – continuous infusion –HTN less than or equal to 100 mcg/kg/min; for ACSless than or equal to 60 mcg/kg/minDOPamine: for telemetry unit less than or equal to5 mcg/kg/minDOBUTamine: for telemetry unit less than or equal to10 mcg/kg/minDepartment Specific Disaster Plan for NJ Cancer CenterPharmacy and UH Main Pharmacy – approvedMr. Emont presented the Pharmacy Department’sdisaster plans for the NJ Cancer Center Pharmacy andMain Hospital Pharmacy.

P&T Update (Continued from page 1)

(Continued on page 3)

The liver plays a prominent role inside the humanbody as the organ for metabolism and detoxification.Under most conditions, the liver will grow back andrepair itself; nevertheless, as my clinical professor oncesaid “the liver is like your best friend, no matter howbad you treat it, it will forgive you; however, once youabuse it to the point of no return, it is gone forever.”The liver is a critical organ that is essential for survivaland the only way to recover from irreversible liverdamage is via liver transplantation. However, long termsurvival even after the operation is not guaranteed andit usually takes around six months to one year toachieve full recovery.2,4 Medication therapy is one ofthe most crucial post-operation procedures that canimprove the patient’s condition and outcome. Thethree general subcategories of medications for postliver transplant patients are the antirejectionmedications, the anti-infective medications, and themiscellaneous medications.

When patients undergo a liver transplant, they mayeither obtain a partial liver from a living donor or a fullliver from a deceased donor, the latter being the more

common. When a patient obtains a liver from a livingdonor, the best option for them is to receive it directlyfrom a family member because this can significantlyreduce the development of an immunologic rejectiontowards the new liver. Liver rejection occurs when theimmune system of the body does not recognize thesurface antigens of the newly acquired organ and theimmune cells start attacking the organ. This can bemanaged with pharmacotherapy by giving patientsanti-rejection medications which are more commonlyknown as immunosuppressants.3 The first lineimmunosuppressant is usually in the corticosteroidclass (ie. methylprednisolone, prednisone).3 In addition,other immunosuppressants that will help in the recoveryprocess include: Prograf® (tacrolimus), Cellcept®

(mycophenolate), Rapamune® (sirolimus), and Neoral®(cyclosporine). When taking these medications, patientsshould be counseled on potential side effects, includingphotosensitivity, increases in blood pressure, anddiarrhea. When patients take immunosuppressants,they should be aware of the increased susceptibility toinfections from bacteria, viruses, and fungi.

Pharmacotherapy Management of Post-Liver Transplant Patients

3

all patients with liver disease. The most important aspectof pharmacotherapy management is patient compliancewith the medications and dietary restrictions. Patientsmust take their medications at accurate times with precisedosing in order to obtain the most benefit out of theirmedication therapy. Lastly, alcohol is a big enemy to theliver; therefore, patients should greatly limit themselvesfrom taking excess amounts of this toxin.4

Contributed by:Michael Feng, PharmD. Candidate of 2014, St. John’s University

References:

1. Jay A. Fishman, M.D., and Robert H. Rubin, M.D., and Robert H.Rubin, M.D. “Infection in Organ-Transplant Recipients.”http://www.nejm.org. The New England Journal of Medicine, 11June 1998. Web. 20 May 2012.<http://www.nejm.org/doi/full/10.1056/NEJM199806113382407>

2. “National Digestive Diseases Information Clearinghouse (NDDIC).”What I Need to Know about Liver Transplantation. Web. 21 May2012.<http://digestive.niddk.nih.gov/ddiseases/pubs/livertransplant_ez/index.aspx>.

3. “Treatment of Acute Cellular Rejection in Liver Transplantation.”Treatment of Acute Cellular Rejection in Liver Transplantation. Web. 21May 2012. <http://www.uptodate.com/contents/treatment-of-acute-cellular-rejection-in-liver-transplantation>.

4. R.M. Weinrieb, and C.P. O’Brien. “Liver Transplantation and SurgeryVolume 3, Issue 3, Arti-cle First Published Online: 30 DEC 2003.”Current Research in the Treatment of Alcoholism in Liver TransplantRecipients. 23 May 1997. Web. 21 May 2012.<http://onlinelibrary.wiley.com/doi/10.1002/lt.500030321/pdf>.

Since liver transplant patients are susceptible toinfections from taking immunosuppressants, they areoften given anti-infective medications to protect thebody from these dangerous microorganisms. Some ofthe anti-infective medications include Bactrim®

(sulfamethoxazole-trimethoprim), Valcyte® (valganciclovir),acyclovir, and nystatin. As stated by The New EnglandJournal of Medicine, the most effective type ofpreventative treatment is giving sulfamethoxazole –trimethoprim (400mg/80mg) in all patients who areable to tolerate this antimicrobial.1

The last category of medications for the liver transplantpatients includes supplements and adjuncts which areused to counteract the harsh adverse effects of theimmunosuppressants and the anti-infectives. For example,vitamin E might be given to reduce the recovery time ofthe surgery and vitamin C might be given to boost theimmune system. Calcium with vitamin D is given toprevent bone density loss. These medications are acrucial part of the pharmacotherapy management andshould not be disregarded.

Patients who are fortunate enough to receive a liverare given a second chance at life. Hence, they shouldtreasure it because this is a rare opportunity not given to

Pharmacotherapy Management (Continued from page 2)

Azithromycin Linked to Cardiovascular DeathThe FDA is currently reviewing data of a study

published in the New England Journal of Medicine thatindicated a link between the use of azithromycin, acommonly prescribed macrolide antibiotic, and anincreased risk of cardiovascular death.1

The study examined a Tennessee Medicaid cohort ofpatients taking five day treatments of azithromycin,amoxicillin, ciprofloxacin, levofloxacin, or no antibiotic.Results showed that there was an increased risk ofcardiovascular death in patients taking azithromycin whencompared to those taking amoxicillin, ciprofloxacin, or noantibiotic, but no difference was found when comparedto patients on levofloxacin. There was no increase in riskof death from non-cardiovascular causes among patientswho took azithromycin, but an increase in risk of deathfrom any cause was noted. This small but definite increasein risk of cardiovascular death was most significant inpatients at high risk for cardiovascular disease.1

Investigators hoped to link the proarrhythmic effects ofazithromycin to an increased risk of sudden cardiac death.Other macrolide antibiotics, including clarithromycin anderythromycin, have previously been noted to havecardiovascular effects. In 2011, the package inserts for

these medications were edited to include warnings for QTinterval prolongation, which could lead to the possiblyfatal abnormal heart rhythm, torsades des pointes.Warnings for QT interval prolongation were added to thepackage insert for azithromycin in March 2012.2

The FDA recommends that healthcare professionals takeinto account the potential for QT prolongation whenprescribing macrolide antibiotics. Furthermore, patientsshould not stop taking azithromycin without contactingtheir healthcare professional. Be on the lookout for furtherinformation as the FDA continues to review the data ofthis study.2

Contributed by:Patrick Lake, PharmD. Candidate 2014, Rutgers University

References:

1 Ray WA, Murray KT, Hall K, et al. Azithromycin and the risk ofcardiovascular death. N Engl J Med. 2012; 366: 1881-90.

2 FDA statement regarding azithromycin (Zithromax) and the riskof cardiovascular death. Food and Drug Administration.http://www.fda.gov/Drugs/Drugsafety/ucm304372.htm.Published 17 May 2012. Accessed 5 June 2012.

4

Atrial fibrillation is the most common arrhythmia affectingapproximately 2.2 million people in the United States. It iscommonly caused by hypertension, coronary arterydisease, heart valve disease, chronic lung disease, heartfailure, cardiomyopathy, congenital heart disease andpulmonary embolism. During atrial fibrillation, the atriacontract rapidly and irregularly, causing blood to pool inthe atria leading to formation of blood clots. Non-valvularatrial fibrillation is atrial fibrillation without any significantproblems in the heart valves. Blood clots may travel to thebrain causing a block in blood flow and leading to a stroke.Symptoms of a stroke include sudden weakness, paralysisof face, arms, or legs, trouble speaking or understandingspeech, or difficulty with vision.1-5

Rivaroxaban is a new orally bioavailable direct factor Xainhibitor that selectively blocks the active site of factor Xaand does not require a cofactor, such as Anti-thrombin III,for activity. On July 1, 2011, rivaroxaban was approved bythe U.S. Food and Drug Administration (FDA) for twoindications: to reduce the risk of stroke and systemicembolism in patients with nonvalvular atrial fibrillation, andfor prophylaxis of deep vein thrombosis (DVT), which maylead to pulmonary embolism in patients undergoing kneeor hip replacement surgery.7-9 In addition, rivaroxaban wasrecently added to The University Hospital formulary withrestrictions to orthopedics, cardiology, and patient’s ownmedications.

Rivaroxaban is metabolized primarily by CYP3A4 andCYP2J2. It is also a substrate of P-glycoprotein (P-gp). Useof rivaroxaban with drugs that are strong inhibitors of bothCYP3A4 and P-gp is contraindicated, such as ketoconazole,ritonavir, and clarithromycin. Administration of inducers ofCYP3A4 or P-gp, such as rifampin, carbamazepine,phenytoin, and St. John’s wort, should be avoided.Rivaroxaban should not be used with otheranticoagulants.7-11

The safety and efficacy of rivaroxaban (Xarelto®) wasassessed in more than 14,000 patients in a multicenter,randomized, double-blind, and double-dummy trial. Inpatients with atrial fibrillation, rivaroxaban was noninferiorto warfarin for the prevention of stroke or systemicembolism. Patients were randomly assigned to receive afixed dose of rivaroxaban (20 mg daily or 15 mg daily inpatients with a creatinine clearance of 30 to 49 ml per

minute) or an adjusted-dose of warfarin (targetinternational normalized ratio [INR], 2.0 to 3.0). In theprimary efficacy analysis, stroke (ischemic or hemorrhagic)or systemic embolism occurred in 188 patients in therivaroxaban group (1.7% per year) and in 241 patients inthe warfarin group (2.2% per year) (CI 0.66 to 0.96;P<0.001 for noninferiority). There was no significantbetween-group difference in the risk of major bleeding,although intracranial and fatal bleeding occurred lessfrequently in the rivaroxaban group.6

Similar to other anticoagulants, rivaroxaban can causebleeding. The most common adverse drug reaction ofrivaroxaban seen in clinical trials was bleeding, whichoccurred more commonly with rivaroxaban than withenoxaparin. However, there is no antidote for rivaroxabanas there is one for warfarin (vitamin K) and enoxaparin(protamine). Since rivaroxaban is highly bound to plasmaprotein (92-95%), it is not dialyzable.7-11

Rivaroxaban is available in 10mg, 15mg and 20mg tabletsand is given orally once daily. Prothrombin time (PT), CBCwith differential, renal function, and hepatic functionshould be monitored. Although in some clinical trials, aPTT,PT/INR, or antifactor Xa levels were not monitored, somepatient populations, such as the renally or hepaticallyimpaired or extremely obese, may need monitoring ofprothrombin time (PT).7-9

In conclusion, rivaroxaban is an oral direct factor Xainhibitor that has safety and efficacy similar to warfarin forthe prevention of stroke in atrial fibrillation patients. It isFDA approved for two indications: reducing risk of strokeand systemic embolism in nonvalvular atrial fibrillationpatients and for DVT prophylaxis in patients undergoingknee or hip replacement surgery. It does not requireroutine monitoring of INR. Rivaroxaban may causebleeding, however, there is no specific antidote available.

Contributed by:Afsheen Khan, Pharm.D. Candidate 2012, RutgersUniversity

References:1. Lloyd-Jones D, Adams R, Brown TM, et al. Heart disease and

stroke statistics 2010 update: A report from the American HeartAssociation. Circulation 2010;121:e1–e170.

2. Atrial Fibrillation [Internet]. Quick Answers to Medical Diagnosisand Therapy; c2012 [cited 2012 Apr 19]. Available from:http://www.accessmedicine.com/quickam.aspx

3. National Heart Lung and Blood Institute [Internet]. U.S. Department

Rivaroxaban (Xarelto®): The New Oral Anticoagulant

5

of Health & Human Services (US); c2011 [cited 2012 Apr 19].Available from http://www.nhlbi.nih.gov/health/healthtopics/topics/af/

4. Sanoski CA, Bauman JL. The Arrhythmias. In: Talbert RL, DiPiro JT,Matzke GR, et. al. Pharmacotherapy: A Pathophysiologic Approach.8th ed. New York: McGraw-Hill; c2011 [cited 2012 Apr 19]. Availablefrom: http://www.accesspharmacy.com/content.aspx?aID=7972803

5. FDA approves Xarelto to prevent stroke in people with commontype of abnormal heart rhythm [Internet]. Rockville (MD): U.S.Food and Drug Administration (US); c2011 [cited 2012 Apr 19].Available from:http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm278646.htm

6. Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus Warfarinin Nonvalvular Atrial Fibrillation. N Engl J Med. 2011,365(10):883-91.

7. Xarelto® [package insert]. Titusville, NJ: Janssen Pharmaceuticals,Inc; 2011.

8. Xarelto. Lexi-Comp OnlineTM, Hudson, Ohio: Lexi-Comp, Inc.;2012; Accessed Apr 19, 2012.

9. Abrams PJ and Emerson CR. Rivaroxaban: A Novel, Oral, DirectFactor Xa Inhibitor. Pharmacotherapy. 2009, 29(2):167-81.

10.Gulseth MP, Michaud J, Nutescu EA. Rivaroxaban: An Oral DirectInhibitor of Factor Xa. Am J Health Syst Pharm. 2008, 65(16):1520-9.

11.Kubitza D, Becka M, Voith B, et al. Safety, Pharmacodynamics, andPharmacokinetics of Single Doses of BAY 59-7939, an Oral, DirectFactor Xa Inhibitor. Clin Pharmacol Ther. 2005, 78(4):412-21.

Anemia due to chronic kidney disease is caused bythe decrease of the hormone erythropoietin. Erythro-poietin is an endogenous hormone necessary for redblood cell production. Ninety percent of erythropoietinis produced and secreted by cells within the kidneys. Aspatients with chronic kidney disease progress towardsend stage renal disease, their kidneys lose the ability toproduce and secrete erythropoietin.

Peginesatide injection is a synthetic erythropoietinreceptor-activating peptide that does not resemble thestructure of erythropoietin as do the other erythropoiesisstimulating agents (ESA), such as epoetin alfa anddarbepoetin alfa. Peginesatide binds to the erythropoietinreceptor and stimulates the production of red bloodcells. Peginesatide is only indicated for anemia in patientsdue to chronic kidney disease that are on dialysis.Peginesatide is not recommended for non-dialysisdependant patients or patients receiving chemotherapy.It is contraindicated in patients with uncontrolledhypertension.

On March 27, 2012 the U.S. Food and DrugAdministration (FDA) approved Omontys® (peginesatide)for the treatment of anemia due to chronic kidneydisease. Peginesatide was approved based on twoPhase 3 randomized, open-labeled, active-controlled,multi-centered trials (EMERALD trial) that tested itssafety and efficacy against epoetin alfa. Between thetwo studies, approximately 1066 patients wererandomized into the peginesatide treatment arm and542 were randomized into the epoetin alfa treatmentarm. Peginesatide and epoetin alfa had a similar abilityto maintain the patient’s hemoglobin between 10-12g/dL. The most common adverse reactions wereshortness of breath, diarrhea, nausea, cough, andarteriovenous fistula site complication. In a pre-specifiedprospective analysis of composite cardiovascular safety

endpoints (death, myocardial infarction, stroke, orserious adverse event, such as congestive heart failure,unstable angina or arrhythmia), 22.8% of peginesatidepatients had at least one of these events and 24.4% ofthe epoetin alpha patients had at least one of theseevents (CI 0.77-1.17).

Peginesatide presents a novel dosing regimencompared to epoetin alfa and darbepoetin alfa. Epoetinis administrated three times a week and darbepoetin isgiven every week or every two weeks. The starting dosefor patients on peginesatide and not currently on ESAsis 0.04 mg/kg as a single intravenous or subcutaneousinjection once monthly. Peginesatide should be initiatedwhen the hemoglobin level is less than 10 g/dL. Due toits similar safety and efficacy to epoetin alfa based onthe EMERALD studies, peginesatide provides aconvenient alternative for dialysis patients that nowhave the option to receive injections once a month ascompared to twelve times a month with epoetin alfa.

Contributed by:Bryan Okwuonu, Pharm D. Candidate 2012

References:

1. FDA New Release: FDA approves Omontys® to treat anemia inadult patients on dialysis. Food and Drug Administration. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm297464.htm. Published 27 March 2012. Accessed 23 April 2012.

2. Omontys®. [package insert]. Deerfield, IL: Takeda PharmaceuticalsAmerica, Inc; 2012.

3. Epogen®. [package insert]. Thousand Oaks, CA: AmgenManufacturing Limited; 2011.

4. Kidney Disease Outcomes Quality Initiative (KDOQI) ClinicalPractice Guideline and Clinical Practice Recommendations foranemia in chronic kidney disease: 2007 update of hemoglobintarget. Am J Kidney Dis 2007;50(3):471–530.

5. Hudson JQ. Chapter 53. Chronic Kidney Disease: Management ofComplications. In: Talbert RL, DiPiro JT, Matzke GR, et al.Pharmacotherapy: A Pathophysiologic Approach. 8th ed. New York:

OMONTYS® (peginesatide) FDA approved for anemiadue to CKD in dialysis-dependent patients

Rivaroxaban (Xarelto®): The New Oral Anticoagulant (Continued from page 4)

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Updated Guidelines Suggest Less Frequent Use ofVitamin K to Reverse Warfarin's Anticoagulation Effects

Warfarin (Coumadin®) is a vitamin K antagonist that iscommonly used for patients that are at an elevated riskof thromboembolism formation. These patients mayhave prior history of deep vein thrombosis or pulmonaryembolism; atrial fibrillation; recent knee or hipreplacement; or one of several types of prosthetic heartvalves. Warfarin acts by interfering with vitamin K,which is necessary to activate other clotting factors.Without these clotting factors, the blood will not clotas efficiently.1 The time that it takes the blood to clot ismeasured by the PT/INR (Prothrombin Time/International Normalized Ratio). When the PT/INRvalue is elevated (normal goal is 2-3 or 2.5-3.5depending on indication), the patient is at a higher riskof bleeding.1 Prior to a recent update by the AmericanCollege of Chest Physicians, patients with INR values of5-9 had a dose of warfarin held and/or they were givenvitamin K.2 Both of these options are often used tolower a patient's INR. Vitamin K is available in an oraltablet, subcutaneous injection, or intravenous infusion.The dose can range from 2.5 to 10 mg orally and up to10 mg intravenously by slow infusion.1 The mostrecent update from the American College of ChestPhysicians suggests decreasing the use of vitamin K,unless the patient is experiencing bleeding.3

According to the CHEST guidelines, patients takingwarfarin with an INR between 4.5 and 9 that do nothave evidence of bleeding should not routinely receivevitamin K. Instead, one to two doses of warfarinshould be held and the INR rechecked. Often timesvitamin K lowers the INR too much and for too long in

these patients.2 Large doses of vitamin K can lead towarfarin resistance for up to a week. Patients with anINR of greater than 9 and no evidence of bleeding arerecommended to receive low-dose oral vitamin K alongwith holding of warfarin. Patients with seriousbleeding or prior to emergent surgery with high INRshould receive 5-10 mg of vitamin K intravenously viaslow infusion.2 Pharmacokinetic data also suggestsagainst the use of vitamin K subcutaneously, as itsabsorption and effects are less predictable than theintravenous route.

Contributed by:Tyler McCamish, PharmD

References:

1. Ansell J, Hirsh J, Hylek E, et al. Pharmacology and management ofthe vitamin K antagonists: American College of Chest Physiciansevidence-based clinical practice guidelines (8th edition). Chest2008;133(Suppl 6):160S-98S.

2. Holbrook A, Schulman S, Witt DM, et al. Evidence-basedmanagement of anticoagulant therapy: antithrombotic therapyand prevention of thrombosis, 9th ed: American College of ChestPhysicians evidence-based clinical practice guidelines. Chest2012;141(Suppl 2):e152S-84S.

3. PL Detail-Document, How to Manage High INRs in WarfarinPatients. Pharmacist's Letter/Prescriber's Letter. May 2012.

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Hospital Formulary Additions and Deletions Jan 2010-April 2012

IV solution no longer available commercially

One purchase within last 3 years

Not available commercially

Not deemed necessary at this time

Manufacturer Discontinued

Manufacturer Discontinued

Not used/orderd in last 2 years

Not used/orderd in last 2 years

Not used/orderd in last 2 years

Not used/orderd in last 2 years

Not used/orderd in last 2 years

Not used/orderd in last 2 years

Not used/orderd in last 2 years

Not used/orderd in last 2 years

Not used/orderd in last 2 years

Similar to Micafungin. Switch would

potentially save up to $25,000/yr

Additional coverage against 6

pneumococcal serotypes

Manufacturer discontinued

Manufacturer discontinued

Manufacturer discontinued

Not deemed necessary for agitation

indication/tabled for psychiatries

Not in use

Not in use

Not in use

550 mg approved not 220mg, alternative

to lactulose for hepatic encephalopathy

Alternative (penicilloyl-polylysine) taken off market

in 2004 (low market) then reintroduced in 2009

Increase gram (+) coverage, increase

ocular penetration, favorable cost

compared to levofloxacin

Addition of Vigamox

Similar efficacy and more cost effective

than beclomethasone

More expensive than fluticasone

($120.36 vs $4.24)

1/20/2010

2/17/2010

2/17/2010

3/17/2010

3/17/2010

3/17/2010

4/22/2010

4/22/2010

4/22/2010

5/19/2010

5/19/2010

5/19/2010

5/19/2010

5/19/2010

5/19/2010

5/19/2010

5/19/2010

5/19/2010

5/19/2010

5/19/2010

6/16/2010

7/21/2010

7/21/2010

7/21/2010

9/15/2010

9/15/2010

9/15/2010

9/15/2010

9/15/2010

9/15/2010

9/15/2010

9/15/2010

10/20/2010

10/20/2010

Symbicort

Azmacort

Talwin

Abbottkinase

Hylenex Recomb

Moban

Ethiodol

Proleukin

Trisenox

Elspar

Myleran

Mylotarg

Cerezyme

Alkeran

Zanosar

Thioplex

Mycamine

Cancidas

Prevnar-13

Pancrease

Attenuvax

Meruvax

Cymbalta

Stelazine

Loxitane

Moban

Xifaxan 550

Prefen

Vigamox

Quixin

Flosase

Qvar

Thrombin Bovine JMI

Budesonide/formoterol fumarate dehydrate

Triamcinolone acetonide

Sodium Chloride 5%

Pentazocin injection

Urokinase

Hyaluronidase Human Injection

Molindone

Ethiodized Oil 37%

Aldesleukin

Arsenic Trioxide

Asparaginase

Busulfan

Gemtuzumab Ozogamicin

Imiglucerase

Melphalan

Streptozocin

Thiotepa

Micafungin

Caspofungin

Pneumoccocal 13 valent conjugate

vaccine

Amylase/lipase/protease

Measles vaccine live

Rubella vaccine

Duloxetine

Trifluoperazine

Loxapine

Molindone

Rifaximin

Benzylpenicilloyl polylysine

Moxifloxacin opthalmic 0.5%

Levofloxacin opthalmic

Fluticasone nasal spray

Beclomethasone

Generic Brand ReasonApproved Denied DeletedP&T Date

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

8

5mg no longer available on market

Low usage

Removed by Anti-infective subcommittee

Removed by Anti-infective subcommittee

Removed by Anti-infective subcommittee

Removed by Anti-infective subcommittee

Removed by Anti-infective subcommittee

Removed by Anti-infective subcommittee

No longer available

Difficultly registering patients with generic

company

Easier registering patients with brand

company

Less monitoring compared to warfarin,

rapid onset, cost effectiveness

Decrease medication errors

Discontinued by manufacturer

Discontinued by manufacturer

Substitution for 15mg/0.6 ml

Less injections than ranibizumab

Comparable/greater efficacy to zoledronic

acid, less monitoring for renal impairment

Class review performed, decrease

amount of formulations

Class review performed, decrease

amount of formulations

Class review performed, decrease

amount of formulations

For code carts and floor stocks

Overdose risk, cost $1 vs $40 /day (oral vs IV)

Higher hepatocyte uptake, shorter time

from administration to imaging

Recent price reduction of Recothrom, no

cost benefit

Once daily dosing; VRE

Strovite unavailability

Levemir cost less than Lantus however

more Levemir is needed to reach Lantus

effectiveness, negating price advantage

First beta lactam to have activity against MRSA,

less expensive than Linezolid and Daptomycin,

more expensive than vancomycin

Not necessary at this time; available as

non-formulary for 20-50 patients /year

Cost advantage over ramipril ($10-28 vs $.24-$1)

More expensive than lisinopril

10/20/2010

10/20/2010

11/17/2010

11/17/2010

11/17/2010

11/17/2010

11/17/2010

11/17/2010

11/17/2010

12/16/2010

12/16/2010

1/19/2011

1/19/2011

1/19/2011

2/16/2011

2/16/2011

3/16/2011

3/16/2011

4/20/2011

4/20/2011

4/20/2011

4/20/2011

5/18/2011

6/15/2011

6/15/2011

6/15/2011

7/20/2011

7/20/2011

9/21/2011

9/21/2011

9/21/2011

9/21/2011

Synthroid

Neosporin

Maxitrol

Neosporin opth drops

Cortisporin

Bleph-10

Blephamide

Clozaril

Pradaxa

Ozurdex

Xgeva

Ofirmev

Eovist

Thrombin JMI

Cubicin

Nephro-vite

Levemir

Teflaro

Samsca

Prinivil

Altace

Glucose 4mg chewable tablets

Levothyroxine 200mcg

Neomycin/bacitracin/polymyxin opth. ointment

Neomycin/polymyxin/dexamethasone

Neomycin/polymyxin/gramicidin

Neomycin/polymyxin/hydrocortisone (drops)

Sulfacetamide sodium (drops)

Sulfacetamide/prednisolone (drops/ointment)

Glucose 5mg chewable tablets

Clozepine (generic)

Clozepine

Dabigatran

Heparin 10,000units/ml

Oxycodone intensol liquid 20mg/ml

Ferrous sulfate 15mg/0.6 ml

Ferrous sulfate 15mg/ml

Dexamethasone intravitreal implant

Denosumab

Magnesium Ig/lOOmI D5W

Magnesium 4mEq/ml in 10 ml vial

Magnesium 4mEq/ml in 20 ml vial

Magnesium 2g/50ml Sterile water

Acetaminophen intravenous

Gadoxetate disodium

Thrombin

Daptomycin

Multivitamin (renal)

Insulin Detemir

Ceftaroline

Tolvaptan

Lisinopril

Ramipril

Generic Brand ReasonApproved Denied DeletedP&T Date

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

Hospital Formulary Additions and Deletions Jan 2010-April 2012 (cont.)

9

ISMP recommendation to provide ready to

use formulation; code carts only

2010 ACLS code guidelines alternative to

procainamide and amiodarone

Line extension from Oncology Sub committee

Manufacturer changed concentration from

12mg/ml

Manfacturer changed concentration to

3.6-15mg from 3mg menthol

Manufacturer discontinued

Manufacturer discontinued 12mg/ml oral liquid

Manufacturer discontinued all strengths

Manufacturer discontinued

First line for chronic lymphocytic

leukemia and non-hodgkin’s lymphoma

Withdrawn from market due to

PROWESS-SHOCK study

UH formulary is 10mg/ml

Adacel has comparable efficacy and costs less

Comparable efficacy to Warfarin, less monitoring;

restricted to FDA approved indications

Limited data, await additional studies

Preparation is preferrableto RabAvert, more

cost effective

Imovax cost less/ easier preparation

Low and inappropriate usage

Inappropriate usage, recommended use of

Td vaccine

Amphadase 150units/ml no longer on market

Amphadase 150units/ml no longer on market

High cost, oral therapy available

Oral valganciclovir preferred

Surgery is mainstay of therapy, denied until

more evidence suggests Xiaflex usage

Comparable efficacy to Meropenem but more

expensive

Lower incidence of respiratory depression,

constipation, and abuse

Reversible P2Y12 receptor inhibitor demon-

strated faster onset and offset, and lower

incidence of death from vasular causes. Ml,

and stroke when compared to Clopidogrel and

Prasugrel

9/21/2011

9/21/2011

10/19/2011

10/19/2011

10/19/2011

10/19/2011

10/19/2011

10/19/2011

10/19/2011

11/16/2011

11/16/2011

11/16/2011

12/21/2011

12/21/2011

12/21/2011

1/18/2012

1/18/2012

1/18/2012

1/18/2012

2/15/2012

2/15/2012

2/15/2012

2/15/2012

3/21/2012

4/12/2012

4/18/2012

4/18/2012

Nexterone

Emend

Tamiflu

Cepacol

Treanda

Xigris

Paregoric

Boostrix

Xarelto

Eylea

Imovax

RabAvert

DT

Hylenex

Amphadase

Zovirax

Xiaflex

Primaxin

Ultram

Brilinta

Amiodarone IV 150mg/100ml

D5W

Sotalol IV

Fosaprepitant dimeglumine injection

Oseltamivir 6mg/ml

Menthol-benzocaine 3.6-15mg

Neomycin

Oseltamivir 12mg/ml

Thiopental sodium

Menthol 3 mg

Bendamustin

Drotrecogin alpha

Camphorated opium tincture 2mg/5ml

Tdap (tetanus toxoid, reduced diphtheria

toxoid, and acellular pertussis)

Rivaroxaban

Aflibercept

Rabies vaccine

Rabies vaccine (avian)

Diphtheria, tetanus toxoid

Tetanus toxoid

Hyaluronidase Human Injection 150 units/ml

Hyaluronidase bovine injection

Acyclovir ointment

Oral ganciclovir

Collagenase clostridium histolyticum

Imipenem/cilastatin

Tramadol

Ticagrelor

Generic Brand ReasonApproved Denied DeletedP&T Date

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

Hospital Formulary Additions and Deletions Jan 2010-April 2012 (cont.)

10

Blockbuster Drug, Plavix®, Goes Generic

Underdosing of Antibiotics in Obese Patients

Plavix® (clopidogrel bisulfate, Bristol-Myers), one ofthe world’s bestselling medications, went generic onMay 17, 2012. Clopidogrel, a blood thinner, is Foodand Drug Administration (FDA) approved to treatpatients who have had a recent heart attack, stroke, orhave partial or total blockage of an artery.1 Clopidogrelhas been known as a drug of “major historicalsignificance” because it was the first drug shown toreduce the risk of heart attack and mortality in a widerange of patients when taken concomitantly withaspirin.2

Generic drugs approved by the FDA have the samequality and strength as the brand-names, thus creatingalternative and affordable treatment options foruninsured patients. Three generic companies havegained FDA approval for clopidogrel 300 milligram(mg) and seven companies for the 75 mg strength.2

Back in 2006, Canadian manufacturer Apotexreleased generic clopidogorel priced 20% lower thanthe branded Plavix®. Sales of the generic drug werehalted until a patent infringement claim by BristolMyers was resolved. After suffering a huge financialloss, BMS won an injunction that would grant Plavix®

market exclusivity and keep the generic version off the

market until the patent expired in May 2012.3,4

The approval of lower-cost generic clopidogrelbenefits patients without health insurance, especiallythose with chronic health problems, as a cost effectivetreatment option.1 Generic clopidogrel will continue tobe a crucial part of cardiovascular therapy, and helpimprove compliance in patients who are unable toafford branded Plavix®.2

Contributed by:Arti Desai, Pharm D. Candidate 2014, Rutgers University

References:

1. Kesselheim AS, Murtagh L, Michelle MM. “Pay for Delay”Settlements of Disputes over Pharmaceutical Patents. N Engl JMed 2011; 365:1439-1445.

2. Shuchman, Miriam. Delaying Generic Competition—CorporatePayoffs and the Future of Plavix. N Engl J Med 2006; 355:1297-1300.

3. U.S Food and Drug Administration. [homepage on the internet].[Updated 2012 May 17; accessed 2012 June 5]. Available from:http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm304489.htm

4. O’Riordan, M. (2012, May 16). So Long, Plavix, What a Ride!Clopidogrel Patent Expires.http://www.medscape.com/viewarticle/764052. Accessed[06/05/12]

One out of every three people in the United States iscurrently considered obese (Body Mass Index BMI ≥30kg/m2). This equates to almost 30 million Americans,with numbers steadily increasing. The immense impactof obesity on healthcare can be seen through theincreasing prevalence of type II diabetes and frequentinadequate dosing of certain antibiotics in hospitals.According to one study presented at a recent annualmeeting of the Society of Critical Care Medicine (SCCM),overweight patients in the emergency department aremore likely to receive subtherapeutic doses of a commonantibiotic, vancomycin. Another study demonstratedthe repeated underdosing of three antibiotics(cefepime, cefazolin, and ciprofloxacin) in obese patients.Poor dosing increases the risk of treatment failure,unnecessary use of broader-spectrum antibiotics, anddevelopment of resistant pathogens.

Vancomycin, one of the most commonly usedantibiotics in the emergency department, has a verynarrow therapeutic index, and if not dosed appropriately,can potentially harm the patient. Various studies have

observed a substantial incidence of inadequate dosingamong the obese. One study concluded that for each10 kg increase in patient weight, patients were tentimes more likely to be underdosed.1 Anothermulticenter, retrospective cohort study evaluatedvancomycin dosing in randomly selected groups stratifiedby body mass index. They found that only 27.7% ofpatients considered obese achieved adequate initialdosing (≥10 mg/kg/dose); moreover, pharmacists failedto correct the inadequate dosing because only 3.3% ofpatients receiving less than the adequate dose had achange in regimen during the first 24 hours of therapy.The study illustrated that “obese patients routinelyreceived inadequate empiric vancomycin using lenientassessment of dosing.” It suggested that greater effortsbe taken to ensure correct weight-based dosingbecause inadequate dosing may potentially lead tosubtherapeutic concentrations and worse clinicaloutcomes.2

(Continued on page 11)

11

(Continued on page 12)

Cefepime, cefazolin, and ciprofloxacin are alsoantimicrobials commonly administered in the emergencydepartment. A retrospective study at a trauma centerdemonstrated that among the obese patients (>100kg)only 8% given cefepime, 3% given cefazolin, and 1%given ciprofloxacin were administered the appropriatedose. The study concluded that emergency physiciansfrequently underdosed common antibiotics in obesepatients, and the risks of undertreated infections includeincreased morbidity, length of stay, and antibioticresistance; therefore, “education on the importance ofappropriately dosing antibiotics for obese patients isneeded.”3

Inadequate antibiotic dosing in the obese populationmay contribute to why patients have poorer outcomesafter surgery and/or during infection. It may also play arole in the growing antibiotic resistance. Atsubtherapeutic levels, a bug may only be partially“knocked out” and return with resistance to thatantibiotic. Undertreated infections increase length ofstay as well, which increases healthcare costs. In orderto diminish the occurrence of poor dosing among theobese, we should not only educate pharmacists and

physicians on the importance of appropriately dosingantibiotics, but also stress the importance ofimmediately correcting inadequate doses. Moreover,not only should we educate the health carepractitioners, but we should also stress the significanceof weight loss to the patients.

Contributed by:Jeanna Shim, Pharm.D Candidate 2014, St. John's University

References:

1 O'Rourke, Kate. "Overweight Patients Often Dosed Inaccurately inEDs." Pharmacy Practice News 39.2011 May.

2 Hallii, R., K. Payne, A. Bain, A. Rahman, S. Nguyen, S. Eaton, A.Busti, S. Vu, and R. Be-dimo. "Multicenter Evaluation ofVancomycin Dosing: Emphasis on Obesity." The American Journalof Medicine 121.6 (2008): 515-18. .

3 Roe JL, Fuentes JM, Mullins ME. “Underdosing of common antibioticsfor obese patients in the ED.” Am J Emerg Med. 2011 Dec 12.

4. O’Riordan, M. (2012, May 16). So Long, Plavix, What a Ride!Clopidogrel Patent Expires. http://www.medscape.com/viewarticle/764052.Accessed [06/05/12]

Underdosing of Antibiotics in Obese Patients (Continued from page 10)

Linagliptin (Tradjenta®) Effective In Black Adults With Type 2 DiabetesIn a recent study conducted by Dr. James Thrasher,

linagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor,was shown to improve glycosylated hemoglobin(HbA1c) in black patients with type 2 diabetes. This isthe first study of a DPP-4 inhibitor to be conductedspecifically in black patients.1 The result of this study isof a particular interest to the staff in our hospital sincepeople of African American descent comprise morethan half of Newark residents.2

The risk of diabetes diagnosis is 77% higher in blackpatients than white patients.3 However, black patientsare often underrepresented in clinical trials, soresearchers decided to perform the study solely onblack patients. This multi-center, double-blinded, andrandomized study consisted of 226 black patients whowere treatment-naïve or on ≤1 oral antidiabetic drug.These patients were divided into a placebo group anda linagliptin group which received 5mg of linagliptinper day. By 24 weeks, the linagliptin group showedsignificantly reduced HbA1c compared to the placebogroup. In addition, the frequency of adverse events in

the linagliptin group was similar to that in placebogroup. Serious adverse events were rare in bothgroups, and most adverse events were unrelated to thestudy drug.1

DPP-4 inhibitors are relatively new; prior tolinagliptin’s approval, two other DPP-4 inhibitors(sitagliptin and saxagliptin) had been approved withinthe last decade. Medications in this class work byinhibiting DPP-4, thus blocking the degradation ofglucagon-like peptide-1 and increasing glycemiccontrol. Consequently, there is less risk of hypoglycemiawith linagliptin compared to that with insulin andsulfonylureas. In addition, patients can take DPP-4inhibitors orally once daily and this class of medicationdoes not affect body weight significantly.4 Kidneyseliminate the majority of the other two DPP-4inhibitors, but linagliptin is not eliminated by thekidneys. As a result, this is a huge advantage forpatients with renal failure since they can take linagliptinwithout dose adjustment.5,6,7

Just that time again to announce the Pharmacy Department’sEmployee of the Quarter, and this time Tyler McCamish steps into the spotlight to receive Pharmacy’s Essential Piece Award. Tyleris one of the newest additions to the Pharmacy Staff, and hasdemonstrated to be such a remarkable professional. Some mayrecall Tyler being featured in an earlier edition of the PharmacyNewsletter, as he was introduced to The University Hospitalcommunity as the Pharmacy Department’s newest StaffPharmacist. Many may have read some of his articles, as Tyler has

contributed very informative pieces to The University Hospital audience who reads each Newsletter edition. Tylerworks the third shift, and sets the example by his great work ethic. Each night, Tyler never fails at giving his bestperformance, a combination of hard work, dedication, and determination in providing true customer satisfaction.Tyler exhibits such a passion for the profession; he is definitely in the rightfield and enjoys what he does. His colleagues enjoy having him as a part ofthe Night Shift, for he is a great team player who will contribute to gettingthe job done with excellence. Being an addition to night staff, he has reallycomplemented the shift very well; he has quickly adapted and has easilyblended in with such a harmonious group. Tyler joined UMDNJ in Septemberof last year, and from day one has really been doing a phenomenal job atworking towards ensuring the finest care for our patients at UMDNJ. Tyleralways exhibits a great attitude and an upbeat demeanor. His pleasantdisposition is very captivating and those who seek Pharmacy’s services lookforward to his support with medication therapy or resolution of potentialissues related with patient care. Get to know Tyler, you’ll be amazed at hisintelligence, integrity, and compassion; he truly is an exceptional individualcommitted to being of service to those who seek his assistance. You willabsolutely love his upbeat attitude and genuine personality. Join us all incongratulating Tyler McCamish as he receives Pharmacy Department’s mostdistinguished honor. Tyler, it is definitely a pleasure having you on staff; yourpresence has been very essential to helping the Pharmacy provide the higheststandard of care to our patients served here at The University Hospital.

Contributed by:Harry Cuartas, Lead Pharmacy Technician

12

In conclusion, linagliptin is a safe and effectivetreatment for type 2 diabetes patients including AfricanAmerican patients. It should be considered as a part ofdiabetes treatment regimen especially in patients withrenal impairment.

Contributed by:Patrick Lake, PharmD. Candidate 2014, Rutgers University

References:

1 Horton E, Mohamed KS, Figaro MK. Randomized, placebo-controlled, double-blind, 24-week study of linagliptin 5mg/day inblack/African American patients with type 2 diabetes [abstract].In: American Association of Clinical Endocrinologist 21st AnnualScientific and Clinical Congress; 2012 May 23-27; Philadelphia,PA. p A26. Abstract #206.

2. State & County QuickFacts. U.S. Census Bureau. January 31, 2012.http://quickfacts.census.gov/qfd/states/34/3451000.html.Accessed June 5, 2012.

3. 2011 National Diabetes Fact Sheet. Centers for Disease Controland Prevention. May 23, 2011.http://www.cdc.gov/diabetes/pubs/estimates11.htm#4. AccessedJune 5, 2012.

4. Davidson, Jaime. Incorporating incretin-based therapies intoclinical practice: differences between glucagon-like Peptide 1receptor agonists and dipeptidyl peptidase 4 inhibitors. Mayo ClinProc. 85(12 Suppl):S27-37, Dec 2010.

5. Sitagliptin. Drug Facts and Comparisons. Facts & Comparisons[database online]. St. Louis, MO: Wolters Kluwer Health, Inc:August 2010. Accessed June 5, 2012.

6. Saxagliptin. Drug Facts and Comparisons. Facts & Comparisons[database online]. St. Louis, MO: Wolters Kluwer Health, Inc:February 2012. Accessed June 5, 2012.

7. Linagliptin. Drug Facts and Comparisons. Facts & Comparisons[database online]. St. Louis, MO: Wolters Kluwer Health, Inc: May2011. Accessed June 5, 2012.

Linagliptin (Tradjenta®) Effective In Black Adults With Type 2 Diabetes (Continued from page 11)