Volume 22, Number 10 November/December 2008 Drugs & Therapy B � U � L � L � E � T � I � N

POLICIES AND PROCEDURES FORMULARY UPDATE The Pharmacy and Therapeutics Med reconciliation: There ARE reasons Committee met October 21, 2008. No drugs were added in or deleted to discontinue some home meds from the Formulary. 2 drugs were policy on Pharmacy Medication verified and corrected (if necessary) designated nonformulary and not A Reconciliation was passed by the home medication profile will be placed available, and 2 restrictions were P&T Committee at the October meet- in the patient’s chart. initiated. ing. This policy continues to improve Further changes to the current pro- our current medication reconciliation cess include a list of situations in which processes, which includes roles for the apparent discrepancies between the ◆ ADDED medical, nursing, and pharmacy staffs home medication profile and the inpa- and helps meet the Joint Commission’s tient profile are considered reconciled None (TJC’s) National Patient Safety Goals (see Table). A call to the prescriber is (NPSGs). not needed to resolve these apparent ◆ DELETED Recently, TJC changed the wording discrepancies between the patient’s None of the medication reconciliation NPSGs home medications and their admission to require “documentation” of the medications. There are situations when ◆ NONFORMULARY AND medication reconciliation process. Upon home medication should be stopped. NOT AVAILABLE admission to Shands at UF, a nurse inter- For example, bisphosphonate medica- views the patient or the patient’s family tions are taken at home, but not contin- Ibuprofen Lysine (NeoProfen®) members to generate a list of all medica- ued in the hospital; or warfarin is taken Lidocaine-Tetracaine Transdermal Patch (Synera®) Table: Discrepancies with Home Medications Considered “Reconciled” ◆ CRITERIA-FOR-USE CHANGES Bisphosphonates – Stopped during hospitalization for safety reasons Factor VIIa, Recombinant Antidiabetic Meds (oral & injectable) – Replaced with insulin infusion (NovoSeven® RT)* Antidiabetic Meds (oral & injectable) – Stopped because patient NPO Blood Pressure Meds – Replaced with IV vasoactive agents in ICU (except diltiazem or *Comprehensive criteria for use approved & must be ordered on a verapamil, which may interact with selected meds [eg, tacrolimus]). Recombinant Factor VIIa Order Form Diuretics – Stopped when admitted to an ICU Warfarin or Antiplatelet Drugs – Stopped for surgery or bleeding diagnosis ® Tretinoin (Vesanoid )† (eg, GI hemorrhage) †Added in the Chemotherapy Policy Metformin – Stopped because of contraindication (eg, elevated serum creatinine) “As Needed” Home Med – Stopped (not necessary) Vitamins or Dietary Supplements – Stopped (not necessary) Ibuprofen lysine is an injectable Nonprescription Meds – Stopped (except daily aspirin) form of ibuprofen with a labeled indi- New Antibiotic Started – Patient admitted for infection cation to close a clinically significant Nonformulary Home Med – Changed to formulary alternative patent ductus arteriosus (PDA) in Scheduled Home Pain Med – Changed to alternative pain control regimen (eg, epidural) premature infants when usual medi- cal management (eg, fluid restriction, tions the patient takes at home. This list at home, but the patient is admitted as diuretics, and respiratory support) is is placed in Smart Chart by the nurse, an immediate pre-operative patient. ineffective. Indomethacin is currently and is accessible under the “medica- The medication reconciliation pro- the pharmacologic agent of choice for tions” tab in NetAccess. A pharmacist cess will be continuously monitored to the treatment of PDA. However, in- then reviews this list and resolves any identify areas for improvement and for domethacin use has been associated discrepancies between the home medi- possible revisions to the criteria. with transient or permanent renal cation list and the current inpatient function impairment, necrotizing medication list. Pharmacists also make enterocolitis (NEC), gastrointestinal ◆ any necessary corrections to the list by (GI) hemorrhage or perforation, and working with the patient’s nurse. INSIDE THIS ISSUE impairment of cerebral blood flow. In the newly approved pharmacy pro- Ibuprofen lysine is purported to be an ◆ Pharmacists & med management cess, documentation of these actions effective alternative to indomethacin will be completed by the pharmacist in ◆ Annual index (continued on next page) the pharmacy information system. The Formulary update, from page 1 disease and pulmonary hypertension. on longer than recommended or with less effects on cerebral, renal, and Since ibuprofen offers no net benefit applying multiple patches simulta- mesenteric blood flow. Although the over indomethacin for the treatment of neously or sequentially could result exact mechanism by which ibuprofen PDA, the P&T Committee designated in systemic absorption sufficient to lysine causes closure of a PDA is not ibuprofen lysine nonformulary and not result in serious adverse events that known, it is believed to be due to the available. are typical of drugs in this class and inhibition of prostaglandin synthesis Synera® transdermal patches are should be avoided. (ie, the same proposed mechanism as a mixture of lidocaine and tetracaine Synera® patches are approximately indomethacin). that provide local dermal analgesia 2.5 times more expensive than LMX® The results of 2 meta-analyses when applied to intact skin by the Cream. The theoretical advantage and recent studies demonstrate that release of its active components into of the 10-minute faster onset (which ibuprofen has similar efficacy to indo- the skin. Lidocaine plus tetracaine is is unproven) and ease of use do not methacin in the closure of PDA. While a “eutectic mixture,” which forms a justify the difference in cost. There- ibuprofen reduces the risk of oliguria, liquid when 2 solids are combined that fore, the P&T Committee designated it may increase the risk for chronic lower the melting point of the combina- Synera® patches nonformulary and not lung disease. No significant differences tion. Synera® has a labeled indication available. were found in the incidence rates of for use in children 3 years of age and Recombinant factor VIIa (rFVIIa) mortality, reopening of the ductus older as well as adults. It is indicated promotes local hemostasis through arteriosus, need for surgical closure, for application to intact skin for 20 to the extrinsic pathway of the coagula- intraventricular hemorrhage (IVH), 30 minutes before superficial venous tion cascade. Factor VIIa complexes NEC, or intestinal perforation. There access and superficial dermatological with tissue factor leading to activa- were also no differences in the dura- procedures such as excision, electro- tion of the coagulation cascade and tion of ventilator support, time to full dessication, and shave biopsy of skin the generation of thrombin, ulti- enteral feeds, or duration of hospi- lesions. mately leading to a stable fibrin clot. talization. No long-term data were Synera® topical patches uses a novel rFVIIa has labeled indications for the reported on neurodevelopmental delivery system consisting of a thin, treatment and prevention of bleeding outcomes. uniform layer of a local anesthetic for- episodes in hemophilia A or B with The most frequently reported mulation with an integrated, oxygen- inhibitors and in acquired hemophil- adverse effects of ibuprofen lysine activated heating component that is ia; treatment of bleeding episodes include sepsis, anemia, IVH, apnea, intended to enhance the delivery of the in congenital FVII deficiency; and, GI disorders, and renal impairment. local anesthetic. The patch begins to prevention of bleeding in surgical Compared to indomethacin, ibuprofen heat once the patch is removed from interventions or invasive procedures has a significantly lower incidence of the pouch and is exposed to oxygen in in congenital FVII deficiency. rFVIIa decreased urine output and increased the air. Of note, the integrated heat- has also been used off-label exten- creatinine. GI perforation and NEC ing component contains iron powder; sively because of its effectiveness in have recently been added to the therefore, the patch must be removed stopping bleeding. Unfortunately, it is Adverse Reactions section of the before a patient undergoes magnetic very expensive and many off-labeled product labeling due to post-market- resonance imaging (MRI). Iron-con- uses are not reimbursed. ing experiences. Contraindications taining products may be a source of Therefore, an ad hoc committee of ibuprofen lysine include untreated magnetic susceptibility artifact. was formed to review the off-labeled infection; congenital heart disease; Synera® patches are similar to other use of rFVIIa and make recommenda- active bleeding (eg, IVH or GI bleed); topical anesthetic agents listed in the tions for its appropriate use in adults. thrombocytopenia; coagulation de- Formulary (eg, LMX® [lidocaine 4%] The Factor VIIa Utilization Commit- fects; suspected NEC; and significant topical cream). The promoted advan- tee used benchmarking data and an renal function impairment. Five cases tages for Synera® over the currently evaluation of the literature to create of pulmonary hypertension have been available products are its ease of use a protocol for appropriate off-label reported after the use of ibuprofen for (ie, peel-and-stick method versus oc- use of rFVIIa. Further, they identified either the prevention or treatment of clusive dressing bandage), Band-aid®- ICD-9 codes for reimbursement in PDA. Because ibuprofen lysine may like packaging, as well as an enhanced specific non-hemophilic uses. An or- decrease renal blood flow, it may delivery of transdermal medication via der form was developed to facilitate interact with other medications that heat activation. It supposedly has a the monitoring of rFVIIa compared undergo renal elimination and may quicker onset of action with a 20-min- with the criteria for use and promote have an additive effect with neph- ute onset as compared to a 30-min- the use of the appropriate ICD-9 rotoxic drugs. Concomitant use of ute onset of action for LMX® Cream codes. rFVIIa must now be ordered corticosteroids may increase the risk (although these agents have not been using this form in adults. of intestinal perforation. compared head-to-head and this is not rFVIIa should not be used for futile Although ibuprofen lysine has a a proven advantage). care, in pregnant patients (unless the lower acquisition cost than indo- There are limited efficacy data for patient has a factor VII deficiency and methacin, due to the stabilities and Synera®. The only published com- in consultation with Hematology), for dosing regimens of ibuprofen and in- parison study did not favor the use prophylaxis (except for the labeled in- domethacin, treating a PDA with ibu- of Synera® over lidocaine infiltration dications), or for disseminated intra- profen lysine is nearly 3 times more in pregnant women prior to epidural vascular coagulation (DIC). It is not expensive than indomethacin therapy insertion. Thus, there are currently no effective in patients with acidosis, in since 3 ibuprofen vials would have to data to support superiority for Synera® patients who are hypothermic (< 35o be used as opposed to delivering all 3 over other available topical anesthetic C), in patients with a platelet count < doses from 1 indomethacin vial. products. 50,000 cells/mm3, or when fibrinogen Although ibuprofen reduces the The most common adverse reactions levels are < 100 mg/dL. risk of oliguria, it is not more ef- are local reactions including erythema, rFVIIa can be used under specific ficacious than indomethacin for the blanching, and edema. These reactions circumstances for trauma, cardiac treatment of PDAs. Ibuprofen may were mild and resolved spontane- surgery, and peri- or post-operative 2 increase the risk of chronic lung ously after treatment. Keeping a patch (continued on next page) Formulary update, from page 2 coagulation profile, platelet adminis- forward will be compared to these bleeding in the Operating Room (OR) tration if platelet count > 50,000, and criteria to determine whether addi- or Critical Care Unit (ICU) setting. cryoprecipitate to replace fibrinogen if tional actions are needed. Emergent Recombinant factor VIIa may be used < 100; and no obvious surgical cause. use will be reviewed retrospectively; for severe multiple trauma patients The initial recommended dose of for non-emergent use, the Hematol- with ongoing bleeding and medical rFVIIa is 45 mcg/kg for surgical use, ogy Service is available for consulta- coagulopathy despite surgical inter- including cardiac surgery. A fixed dose tion. vention and continued infusions of of 5 mg is used for trauma. All doses Tretinoin must now be ordered on plasma (>4 units fresh frozen plasma greater than 1 mg will be rounded to a Chemotherapy Order Form. Tretin- [FFP]) and/or ≥ 10 units of packed the nearest vial size (ie, nearest mil- oin, also known as all-trans retinoic red blood cells (PRBC) in 6 hours, in ligram). acid (ATRA), is a retinoid currently conjunction with the massive transfu- A complete blood count (CBC), fibrin- listed in the Formulary with a labeled sion protocol. It may also be used for ogen, and blood gas (for pH) should be indication for the induction of remis- uncontrolled hemorrhage associated measured before the administration of sion in patients with acute promyelo- with inability to achieve adequate factor VII. A prothrombin time/interna- cytic leukemia (APL). hemostasis for chest closure, and tional normalized ration (PT/INR), acti- The most frequent adverse effects after post-transfusion platelet count vated partial prothrombin time (aPTT), associated with tretinoin are typical and coagulation factors are accept- and thromboelastogram (TEG) may be of the retinoids (eg, headache, skin ably corrected and qualitative clot in considered in select cases. The degree abnormalities [dry skin, pruritus, che- the surgical field remains inadequate of bleeding should be reassessed 20 litis, and xerostomia], bone pain, and with no obvious surgical cause. to 30 minutes after the initial dose of arthralgias). Respiratory toxicities are rFVIIa use to control peri- or post-op- rFVIIa for either resolution of bleed- common. Tretinoin is also a potent erative bleeding in the OR or ICU set- ing or, if excessive bleeding continues, teratogen and should be avoided in ting may be used for rescue therapy redosing or surgical exploration. pregnant patients, although its use for life-threatening ongoing bleeding The criteria for use are voluntary at has been reported in the second and despite other measures to correct this time; however, all rFVIIa use going third trimesters.

MEDICATION MANAGEMENT Pharmacist order review: Exceptions and misconceptions harmacists are the healthcare to the patient, a licensed indepen- proved jointly by both medical staff and Pprofessionals usually responsible dent practitioner (LIP) is available at the Department of Pharmacy Services. for the preparation and dispensing bedside, for a controlled emergency However, a LIP may obtain a contrast of medications. Pharmacists promote department medication list, and for a agent without pharmacist review when good patient care and prevent serious listing of radiology department needs a delay could cause patient harm or medication errors. However, what hap- as deemed appropriate. if the radiologist is at the bedside. A pens when pharmacists do not review Numerous medications are available pharmacist may be available on-call, if medications orders? Is it acceptable to without pharmacist review (“override necessary.2 A sampling of contrast use circumvent the pharmacist? medications”) in automatic dispensing without prior pharmacy review must The Joint Commission (TJC) has cabinets (ie, Omnicell cabinets) for the be done to assure compliance with this Medication Management standards situations specified in TJC standards. standard and to determine if there are (MM.05.01.01) for the selection and A pharmacist does not have to review a opportunities for improvement. procurement, storage, ordering and medication order if a delay would harm The P&T Committee is currently re- transcribing, preparing and dispensing, the patient in an urgent situation, like assessing which medications should be administration, and monitoring of medi- epinephrine for anaphylaxis.1 Thus, listed in the list of “override medica- cations. These standards are intended epinephrine is an “override medica- tions.” TJC standards will determine to increase safety and improve patient tion.” Override medications also may which medications cannot be over- care and mandate that pharmacists be obtained without a pharmacist’s ridden (eg, medications with slow review the appropriateness of all review if a LIP is physically at the onsets of action like transdermal and medication orders for medications dis- patient’s bedside during administra- sustained-release products). pensed in the organization.1 Orders are tion of the medication. A LIP must Medication management stan- assessed for correctness of the medica- control the ordering, preparation, and dards decrease medication errors and tion, dose, frequency, route of adminis- administration of a medication during improve patient safety. The Pharmacy tration, the absence of therapeutic du- critical times. For instance, if a prac- Department has the responsibility plication, and the validity of potential titioner ordered a dose of intravenous to evaluate orders for medications; allergies or sensitivities. In addition, beta-blocker for a patient experiencing however, there are limited exceptions. potential drug and food interactions, tachycardia, he or she is responsible for Shands at UF is continually improving contraindications, laboratory values assessing, preparing, and administer- this process. that may potentially be impacted, and ing the medication. The LIP must be by Abigail A. Dee, PharmD other relevant medication-related is- present physically at the beside…not References sues or concerns must be considered. simply in the vicinity. The practitioner 1. Medication Management. The Joint Commission: Usually pharmacists are in the best po- Updated 10/13/2008. Available: http://www.jointcom- assumes the role of the pharmacist in mission.org/NR/rdonlyres/5B27D3A9-5FE3-44EE-880E- sition to oversee this process. If there these situations. AD6396109592/0/BHC2008MMChapter.pdf.Accessed: are concerns, the pharmacist clarifies TJC has addressed questions 10/22/08. 1 2. Anonymous. Clarifying Information for MM.4.10 and the order with the prescriber. about managing the administration of Rectal Contrast Media. Joint Commission Perspectives The TJC standards list 4 excep- radiopaque contrast agents. Oral and 2006;26(8):9. 3. Guchelaar, HJ, Colen HB, Kalmeijer, MD, et al. Medica�������- tions to these “pharmacist” respon- rectal contrast agents may be adminis- tion errors: hospital pharmacist perspective. Drugs 2005; sibilities. Pharmacists’ duties may tered without prior pharmacist review 65(13):1735-46. be waived if a delay will cause harm under protocols developed and ap- 3 Drugs & Therapy SHANDS NON-PROFIT ORG. B � U � L � L � E � T � I � N Shands at the University of Florida U.S. POSTAGE DRUG INFORMATION SERVICE PAID GAINESVILLE, FL Volume 22, No. 10 Nov./Dec. 2008 PO Box 100316 PERMIT NO. 94 This publication is produced by the Gainesville, FL 32610-0316 Drug Information and Pharmacy Re- source Center under the direction of the Department of Pharmacy Services and the Pharmacy and Therapeutics Committee. EDITOR, DRUGS & THERAPY BULLETIN Randy C. Hatton, PharmD DIRECTOR, PHARMACY SERVICES Alan Knudsen, MS, RPh CHAIRMAN, PHARMACY & THERAPEUTICS COMMITTEE Ricardo Gonzalez-Rothi, MD EDITING, DESIGN, & PRODUCTION Shands HealthCare’s Publication Svcs. © Copyright 2008. All rights reserved. No portion of the Drugs & Therapy Bulletin may be reproduced without the written consent of its editor. FOR MORE INFORMATION, VISIT US ONLINE http://shands.org/professionals/ druginfo/bulletin.asp

2008 Annual index TOPIC...... ISSUE/PAGE(S) TOPIC...... ISSUE/PAGE(S) TOPIC...... ISSUE/PAGE(S) Acebutolol...... July-August/1-2 Fentanyl Transmucosal...... April/2-4 Pentacel®...... October/1,3 Alendronate...... May/1-2 Flebogamma® DIF...... March/1,3 Peppermint Oil...... February/1,3 Allergy Information in the Chart...... April/4 Floxuridine...... April/1-2 Perindopril...... April/2,4 Altretamine...... January/1,3 Fosaprepitant...... September/1-2 P&T Actions 2007...... January/4 Alprazolam ER...... February/1,3 Fosinopril...... April/2,4 Phenytoin Injection...... July-August/5 Ambrisentan...... January/1-2 Fosphenytoin...... July-August/2-4 ...... September/1-2 Anidulafungin...... January/1-2 ...... September/1-2 Pindolol...... July-August/1-2 Anticoagulation Policy, Pediatrics...... September/1 Glycerol, Sterile Anhydrous...... September/1-2 Potassium Replacement...... June/3-4 Aprotinin...... January/1-2 Haloperidol IV...... June/1,3 PRN Orders...... February/1 Aripiprazole ODT...... February/1-2 Heparin, Concentrated...... May/1,3 Procainamide IR & ER...... April/1,3 Armodafinil...... May/1,3 Heparin Shortage...... April/1 Protein C Concentrate...... July-August/2,4 Bendamustine...... September/1-2 Hepatitis B Immune Globulin...... April/1,3 Propranolol...... July-August/2 Benzonatate...... February/1-2 Hexachlorophene Cleanser...... June/1-2 Publication Bias...... March/3-4 Betaxolol...... July-August/1-2 Histrelin Acetate Implant...... July-August/1,3 Quinapril...... April/2,4 Bimatoprost...... June/1-3 Ibandronate Injection & Tablets...... May/2 Ranitidine, Effervescent Tablets...... January/1-3 Bisoprolol...... July-August/1-2 Ibuprofen Lysine...... Nov-Dec/1-2 Ramelteon...... January/1,3 Buckberg Cardioplegia Solution...... February/1-2 Insulin Aspart...... February/1-2 Regadenoson...... October/1-3 Calcitonin Nasal Spray...... July-August/1-3 Insulin Detemir...... March/1-2 Rilonacept...... July-August/2,4 Carbenicillin Indanyl Sodium...... June/1-2 Insulin Pens...... September/3 Risedronate...... May/2 Carbidopa + Levodopa ER...... July-August/1,3 Ipratropium + Albuterol...... June/1-2 Risedronate with Calcium...... May/2 Carteolol...... July-August/1-2 Itraconazole, Intravenous...... January/1-2 Ropinirole...... February/1-2 Carvedilol IR & ER...... March/1,3 Janumet®...... March/1-3 Rotavirus Vaccines...... October/1,3 Caspofungin...... January/1-2 Ketorolac Interactions...... April/1 Samples...... May/1 ...... May/1-2 Kinrix®...... October/1,3 Schedule III Prescriptions...... May/1 Cefotetan...... May/1-2 Lanreotide...... July-August/1,3 Scopolamine Transdermal...... April/1-3 Cefixime...... June/1-2 Latanoprost...... June/1-3 Sitagliptin...... March/1-2 Cefoxitin...... May/2 Lisinopril...... April/2,4 Sliding Scale Insulin...... March/5 Ceftriaxone...... January/1,3 LMX® Cream...... October/2-3 ...... July-August/1 Chlordiazepoxide Injection...... July-August/1,3 Medication Management Standards (TJC)... Nov-Dec/3 Sodium Chloride 7%...... June/1-2 CiproDex®...... September/1-2 Medication Reconciliation...... Nov-Dec/1 Stannous Fluoride...... September/1-2 Colchicine Injection...... February/1,3 Menactra®...... January/1,3 Stress Ulcer Prophylaxis...... January/1,4 Conivaptan Restriction...... October/1-3 Metaxolone...... July-August/1,3 Sulfanilamide Vaginal Cream...... February/1,3 Contraindicated Drug-Drug Combinations... March/1 Methocarbamol...... July-August/1,3 Synera® Patch...... Nov-Dec/1,2 Cromolyn Inhalation Solution...... September/1-2 Modafinil...... May/1,3 Therapeutic Interchange...... September/1,4 Cyclobenzaprine IR & ER ...... July-August/1,3 Moexepril...... April/2,4 Tiludronate...... May/2 Cyclosporine IV...... April/1,3 Nebivolol...... July-August/2 Timolol...... July-August/2 Darunavir...... April/1-2 Nesiritide...... February/1,3 Trandolapril...... April/2,4 Desflurane...... September/1-2 ...... July-August/2,4 Travoprost...... June/1-3 Diphtheria-Tetanus-acellular Pertussis...... May/1-3 New Drugs 2007...... Febrauary/5-6 Tretinoin...... Nov-Dec/1,3 Edrophonium...... May/1,3 Nitroglycerin IV...... April/2-3 Treximet®...... July-August/1,3 EMLA® Cream...... July-August/1,3 NPI Numbers...... July-August/6 Unoprostone...... June/1-3 ...... October/2-3 Oil of Wintergreen...... April/1,3 Varenicline...... March/6 Enlon Plus®...... May/1,3 Orange Book...... October/4 Venous Thromboembolism Prophylaxis...... March/4 Esmolol...... April/2-3 Orphenadrine IR & ER...... July-August/1,3 Vitamin D...... February/4,6 Exenatide...... March/1-2 Patient Own Medications...... July-August/1 Zoledronic Acid...... May/2 Factor VIIa, Recombinant...... May/2-4 Pediarix®...... October/1,3 Zolpidem ER...... March/1,3 4 ...... July-August/5 Penbutolol...... July-August/2 ...... October/1-2 ...... Nov-Dec/1,2-3