Volume 16, Number 3 SHANDS March 2002 at the University of Florida Drugs & Therapy B ◆ U ◆ L ◆ L ◆ E ◆ T ◆ I ◆ N

COST MANAGEMENT FORMULARY UPDATE The Pharmacy and Therapeutics Converting patients from IV Committee met February 19, 2002. 4 drugs were added in the Formu- to PO medications lary. 1 drug was deleted. 3 drugs were designated not available. everal studies have shown that S converting patients from intrave- TARGET DRUGS FOR nous to oral medications can dramati- ◆ ADDED cally decrease hospital costs. Past AUTOMATIC IV TO PO Dexrazoxane studies have found that 50% of ROUTE CHANGE (Zinecard® by Pharmacia patients receiving medications that and Upjohn) Ciprofloxacin Gatifloxacin are equally effective when given Famotidine Pantoprazole intravenously or orally were also on Gemtuzumab ozogamicin Fluconazole Ranitidine (Mytolarg® by Wyeth-Ayerst) ◆ Lansoprazole After a daily screen using the phar- ® Past studies have found (PREVACID by TAP)† macy’s computer system, pharmacists that 50% of patients review patients receiving both intra- Liposomal Daunorubicin receiving medications that venous and oral medications and 1 of (DaunoXome® by Nextar)* are equally effective when the targeted drugs. A pharmacist then reviews the patient’s chart to see if †Suspension & Packets only — given intravenously or Pantoprazole is the oral solid in there is potential to change the patient the Formulary orally were also on other from intravenous to an oral route. oral medications, Patients are considered for conversion *Restricted to ECOG 4999 only — when the following criteria are met. only stocked by the Investigational suggesting they could be • Patient is not NPO. Drug Service switched to oral drugs. • Patient is receiving other oral ◆ DELETED medications. Vidarabine • Patient is not a psychiatric patient ® who refuses oral medications. (Vira A by Parkdale) other oral medications, suggesting • Patient does not have a mechanical they could be switched to oral drugs. ◆ obstruction, such as esophageal NONFORMULARY, These drugs are targeted because the sphincter incompetence or severe NOT AVAILABLE direct cost reduction potential for them ® nausea and vomiting. Diltiazem ER (Cardizem SR is high. • Patient does not have a small bowel by Aventis)‡ If total costs are considered, the syndrome, inflammatory bowel savings are much more. The adminis- Diltiazem ER disease, malabsorption syndrome, or tration-associated costs must be (Dilacor® XR by Watson)‡ any condition that prohibits receiv- considered for intravenous medica- ing medications by mouth. tions. These costs include tubing, Diltiazem ER If the oral route is determined to be ® diluents, time to prepare the medica- (Tiazac by Biovail)‡ appropriate, the pharmacist will place tion, and delivery. The administration an order in the patient’s chart and costs are much less for oral medica- ‡Automatically interchanged to a document the change in the progress ® tions than the administration cost for Cardizem CD generic equivalent notes. The order and the note will be the intravenous medications. noted as a “P&T-Authorized Change.” Dexrazoxane is a parenteral The bioavailabilities of the drugs in this program (see table) are good. chemoprotectant agent used for ◆ reducing the incidence and severity Essentially, the same amount of drug of cardiomyopathy associated with is found in the blood when given INSIDE THIS ISSUE intravenously or orally. There usually the use of anthracycline-based ◆ Pharmacy intranet website chemotherapy regimens. is no reason patients taking oral (continued on next page) medications cannot receive these ◆ Possible Avandia® error drugs orally. Formulary update, from page 1 leukemia (AML). Binding of gemtu- 5 published trials using lansoprazole Dexrazoxane has an FDA-labeled zumab ozogamicin to leukemia cells in pediatric patients to increase indication for use with doxorubicin results in cellular internalization of stomach pH, GERD, and H. pylori administration in women with calicheamicin and cell death. infections. There are several other metastatic breast cancer who have The most recent data documenting published abstracts. Benchmarking received a cumulative doxorubicin the efficacy and safety of gemtuzumab data revealed several pediatric hos- dose of 300 mg/m2. ozogamicin in patients with CD33- pitals that are already interchanging Dexrazoxane has been shown in positive AML in first relapse showed lansoprazole for omeprazole. Also, clinical trials to reduce anthracycline- an overall rate of remission of 30%. lansoprazole suspension is already induced cardiac toxicity in patients The median time to remission was being frequently prescribed to who have already received 300 mg/ 60 days. children at the Shands outpatient m2 of doxorubicin. Several large Bone marrow suppression is the pharmacies because Florida Medic- clinical trials have shown a statisti- dose-limiting toxicity of gemtuzumab aid does not cover omeprazole. cally significant reduction in the ozogamicin. Hepatotoxicity, including Lansoprazole suspension and change of left ventricular ejection veno-occlusive disease (VOD), has packets were added in the Formulary fraction (LVEF) when dexrazoxane been reported in association with and the automatic interchange of was used. gemtuzumab ozogamicin treatment. omeprazole suspension will occur for Although 1 study showed a The cost per dose is approximately all patients greater than 3 years old. statistically significant higher tumor $5000. In a proportion of patients, this Patients on intravenous pantoprazole response rate in patients receiving medication can be administered on (40 mg) who are receiving other doxorubicin plus placebo versus an outpatient basis. However, often medications down a tube, will be doxorubicin plus dexrazoxane, the patients referred to Shands at UF switched to lansoprazole suspension median survival time in the dexra- cannot tolerate outpatient administra- (30 mg). (See Converting Patients zoxane group was nearly double tion. Inpatient reimbursement will not from IV to PO Medications, on page that in the placebo group. Another compensate for the increased cost of 1.) study evaluated the effects of gemtuzumab. For eligible patients, Liposomal daunorubicin is a for- dexrazoxane when treatment was there is an outpatient reimbursement mulation of daunorubicin designed in started after patients received a code, and gemtuzumab should be an attempt to maximize the selectiv- cumulative dexrazoxane dose administered in the outpatient setting ity of daunorubicin for solid tumors of 300 mg/m2. It showed that the whenever possible. Gemtuzumab was in situ. In the circulation, liposomes beneficial effects persisted despite added in the Formulary for use in help to protect the entrapped the delay in administration. There- patients with CD33-positive AML daunorubicin from chemical and fore, it is prudent to delay therapy who are refractory to or intolerant enzymatic degradation, minimizes until a patient has received 300 to conventional chemotherapy. protein binding, and generally mg/m2. Lansoprazole is an oral proton- decreases uptake by normal tissues. Dexrazoxane was associated with pump inhibitor (PPI). It is as effective The specific mechanism by which hematological toxicity in clinical as other oral (ie, omeprazole, panto- liposomal daunorubicin is able to trials. Patients experienced lower prazole, rabeprezole, and esome- deliver daunorubicin to solid tumors WBC nadirs during the 2 weeks prazole) and parenteral (ie, panto- is not known. Liposomal daunorubi- following administration of dexra- prazole) PPIs. The P&T Committee has cin has a labeled indication for zoxane. Patients also had a lower previously designated PPIs therapeuti- Kaposi’s sarcoma in patients with platelet count; however, no patients cally equivalent and has approved the advanced HIV disease. suffered greater than grade 1 therapeutic interchange to the pre- Liposomal daunorubicin is re- toxicity. Nonhematological effects ferred products listed in the Formu- stricted to use only in a specific included pain at the injection site. lary. Pantoprazole remains the only clinical trial. This trial (ie, ECOG Dexrazoxane was added in the intravenous PPI and is listed in the 4999) is a 4-arm protocol for the Formulary for the prevention of Formulary. Oral pantoprazole is the treatment of relapsed acute myelo- cardiac toxicity in adult patients oral solid PPI listed in the Formulary. cytic leukemia (AML). The 4 arms who have received 300 mg/m2 of an Lansoprazole suspension and are: intermediate dose cytarabine anthracycline cytotoxic agent and packets (ie, 15- and 30-mg doses) will (IDAC) + gemtuzumab; IDAC + who would benefit from additional now replace omeprazole suspension in liposomal daunorubicin; or, cyclo- treatment. The estimated cost of the Formulary for all patients greater phosphamide-mesna + IDAC + dexrazoxane for a course of chemo- than 3 years of age. Omeprazole sus- topotecan. Currently, there are no therapy is approximatley $650. pension will continue to be available, published clinical trials to support Dexrazoxane may be considered but will be restricted to patients less the use of liposomal daunorubicin for pediatric patients who have than 3 years of age. All other PPIs for refractory AML. This study is received 300 mg/m2, will continue remain nonformulary and not avail- designed to help determine whether doxorubicin therapy, and who are able. this is an appropriate indication. not eligible to participate in ongoing Lansoprazole suspension is The cost of liposomal daunorubicin dexrazoxane clinical trials. more than 90% less expensive than for an average patient is approxi- Gemtuzumab ozogamicin is an omeprazole suspension. Also, the unit mately $4000 per cycle. The patient antibody-targeted chemotherapy dose powder packet for reconstitution or their insurance company will pay agent. It is a conjugate of a cytotoxic decreases workload and can be for the cost of the medication. The agent (ie, calicheamicin) linked to stocked in SureMed® cabinets for informed consent for this trial a humanized antibody against the better access. discloses this increased cost. CD33 antigen. CD33 antigen is Initially, lansoprazole suspension Liposomal daunorubicin will be expressed on the surface of normal will not be automatically interchanged stored only with investigational drug committed human colony-forming in children less than 3 years of age inventory to assure proper use and to cells and on leukemia cells of most because of the limited amount of data prevent medication errors. There is patients with acute myelocytic published in this age range. There are (continued on next page) 2 Formulary update, from page 2 on the market. Cardizem® SR and its Cardizem® CD potential for confusion between generic equivalents are dosed twice has the least peak-to-trough fluctua- liposomal and regular daunorubicin a day. The other products, (ie, Cardi- tion. and between liposomal doxorubicin zem® CD, Dilacor® XR, and Tiazac®) are As long as a beaded-capsule is (Doxil®) and liposomal daunorubicin. given once a day. Cardizem® CD and available for use in small children, a Vidarabine (adenine arabinoside Dilacor® XR have generic equivalents twice-a-day product is not needed in or Ara-A) is an antiviral drug with and Tiazac® generics are anticipated the Formulary. Having both twice-a- activity against herpes viruses. It has soon. day and once-a-day products avail- been discontinued by its manufactur- These various products create able could lead to medication errors. ers. There are alternative antiviral problems because they are not Therefore, Cardizem® CD or a agents listed in the Formulary. generically equivalent (ie, “bio- generic equivalent of Cardizem® CD Diltiazem ER is any dosage form equivalent”) to each other. Each was chosen and all other products of extended-release diltiazem. The product has a different sustained- will be interchanged to this product. FDA does not differentiate among release mechanism. Although the The once-a-day products will be the different extended-release pharmacokinetics of the once-a-day interchanged on a milligram-per- diltiazem products when listing products are not identical, they are milligram basis. If Cardizem® SR is generic names. There are 4 ex- close and are considered clinically ordered, the dosage will be doubled tended-release diltiazem products equivalent by many practitioners. and changed to an order for once-a- day administration.

NEWS New pharmacy intranet site launched he new Shands intranet, MedIC, The website is packed with useful for the various areas of the depart- T was launched at the end of information that can help answer ment. For example, there is contact January. MedIC stands for Medical questions about drug therapy or the information for the various clinical Information Center. It represents a Department of Pharmacy Services. If specialists, the P&T Committee, and new look, organization, and rules for you cannot find the information that the Outpatient Pharmacy. the Shands intranet. You can access you want on the website, there is The navigation bar at the far left the site from any Shands or UF com- contact information, including email provides links that help the user move puter at http://intranet.shands.org/. addresses and telephone numbers, around the site. This navigation bar is The Shands at UF Department of which should direct you to someone designed to provide the most used Pharmacy Services was 1 of the first who can help you find the information links at the top and provide an outline departments to adopt the MedIC that you need. for the information that is available in structure. The new website can be The figure shows the Department of the site. The major sections are Drug found at http://intranet.shands.org/ Pharmacy Services’ homepage. The Information, The Formulary, The P&T pharm/menu.htm. homepage contains News and An- Committee, The Outpatient Pharmacy, nouncements and contact information and Pharmacy Department Tools. (continued on next page)

3 Drugs & Therapy SHANDS NON-PROFIT ORG. U.S. POSTAGE B ◆ U ◆ L ◆ L ◆ E ◆ T ◆ I ◆ N Shands at the University of Florida DRUG INFORMATION SERVICE PAID GAINESVILLE, FL Volume 16, No. 3 March 2002 PO Box 100316 PERMIT NO. 94 Gainesville, FL 32610-0316 This publication is produced by the Drug Information and Pharmacy Resource 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 2002. All rights reserved. No portion of the Drugs & Therapy Bulletin may be reproduced without the written consent of its editor.

MEDICATION ERROR PREVENTION ® News, from page 3 peutic Interchanges, Shortages, and Avandia or The popular drug information the forms that can be used to request reference Clinical Pharmacology that a drug be added in the Formu- 2000 (CP 2000) is the first link on the lary. Recent changes in the Formu- Coumadin? navigation bar. A link to the Drug lary can be found at Recent Updates. Information Center, where you This is essentially the same informa- onfusion has been reported directly submit questions, is second. tion that is found in the Formulary C between poorly handwritten A page of useful drug information Update section of the Bulletin. ® orders for Avandia (rosiglitazone), an links is next. The current and back If you are having trouble navigat- ® anti-diabetic agent and Coumadin issues of the Drugs & Therapy Bulle- ing the intranet, remember the (warfarin). Although it is difficult to tin are also available. Soon, an up- Search MedIC box. This allows you imagine why the 2 names would be dated version of the popular Pediat- to search the entire intranet. If you confused, they can look alike when ric Dosing Guide will be posted. are trying to remember when or if a handwritten. As the figure shows, The first link under The Formulary drug was added in the Formulary, confusion is possible. Is this order is Drugs Listed in the Formulary. simply type the drug’s name in the ® (from another hospital) for Avandia This page allows the user to deter- box and hit search. This can be ® or Coumadin ? mine whether a medication is readily done from any page, including the Both medications are available in available for use at Shands at UF. A main MedIC page. This will avoid 2-mg and 4-mg strengths. The usual radio button will enable searches by clicking multiple links to find a page. dosage frequency is daily for both Therapeutic Class or Generic-Brand There are many more resources drugs. Clearly written orders will help Name. This search page has been on the Pharmacy Services website. avoid an error. Consider printing these enhanced to allow the user to type in Please take a few minutes to familiar- orders. the first few letters of a drug name ize yourself with the resources into the search box. Once the drug provided. More enhancements are is found, hit enter, and the dosage planned for the near future includ- forms and cost of each item will be ing information on investigational displayed. Please remember that we drugs and protocols and recommen- list common brand names so that dations for formulary alternatives to listing can be located. This does not drugs not listed in the Formulary. mean that that particular brand is If you have questions or com- available. Drugs are listed in the ments about the Department of Formulary as generic entities. Pharmacy Services website, please Also, listed under The Formulary e-mail [email protected]. are links for Restricted Drugs, Thera- 4