Volume 19, Number 10 November/December 2005 Drugs & Therapy B � U � L � L � E � T � I � N

MEDICATION SAFETY FORMULARY UPDATE The Pharmacy and Therapeutics Slang terms and jargon can Committee met October 18, 2005. 4 products were added in the Formulary cause medication errors and 2 were deleted. 1 was evaluated and designated nonformu- his month “Magic ” ents. An screen would not be lary and not available, and 2 drugs T was deleted from the Formulary done, unless the individual ingredients were evaluated, but not added. Criteria (see Formulary Update). The P&T are appreciated. for use were modifi ed for 3 drugs. Committee took this action for medica- Magic Mouthwash will no longer be tion safety reasons. This continues the dispensed at Shands UF because there ◆ ADDED policy of not allowing the use of non- is no evidence that it works better than specifi c terms for mixtures that have a plain saline rinse. Clozapine Tablets traditionally been used. This action follows the banning of (generic by IVAX) Terms like “Magic Mouthwash” are the term “Butt ” several years Glutaraldehyde 0.6% slang, jargon, or coined phrases for ago. Like Magic Mouthwash, Butt Paste (compounded) mixtures that have a specifi c purpose. is a nonspecifi c mixture of ingredients. Levofl oxacin In this instance, the “magic” is pain The “Butt Paste” mixture contained (Levaquin® by Ortho McNeil)* reduction in patients who have muco- Questran Light® (cholestyramine) in sitis of the mouth. Mucositis is a very Aquaphor®. The theory is that the cho- Ondansetron Tablets ® painful condition in patients receiving lestyramine binds bile acids that may (Zofran by GlaxoSmithKline) aggressive cytotoxic chemotherapy. contribute to perineal dermatitis. There *Restricted to ID approval The logic behind Magic Mouthwash are only case reports supporting the was to combine ingredients with use of this mixture. ◆ DELETED different potential mechanisms of ac- Some mixtures for “Butt Paste” Estradiol Valerate (generic) tion. The Magic Mouthwash mixture contain antifungals (eg, clotrimazole) or Magic Mouthwash that has been used at Shands at UF different protectants (eg, karaya gum). (compounded)** contained lidocaine viscous as a local There is even a commercially available anesthetic, (Benad- product call Boudreaux’s Butt Paste® **Nonformulary and not available, ® effective December 1, 2005 ryl ) elixir as another local anesthetic, that contains boric acid, castor oil, min- and nystatin as an antifun- eral oil, zinc oxide, and peru balsam. ◆ NONFORMULARY AND NOT gal. The most commonly used Magic Orders written for “Butt Paste” are not AVAILABLE Mouthwash contains equal parts of valid and will not be dispensed. Zinc Clozapine Orally-Disintegrating lidocaine viscous, diphenhydramine oxide ointment is recommended as an Tablets elixir, and aluminum-magnesium alternative. ® (FazaClo by Alamo hydroxide (Maalox®). The antacid was Other coined terms should also be Pharmaceuticals) included as a protectant. This “lido- avoided. A “Banana Bag” is any varia- ◆ EVALUATED, BUT NOT ADDED benalox” or BMX (Benadryl-Maalox- tion of intravenous dextrose and/or Xylocaine) mouthrinse is “swished and sodium chloride with multiple vitamins, Duloxetine swallowed” or “swished and spit.” thiamine, folic acid, plus-minus magne- (Cymbalta® by Eli Lilly) Unfortunately, there is no standard sium, and/or potassium. This mixture is Mycophenolate Extended- for Magic Mouthwash. Some versions also sometimes referred to as a “Rally Release (Myfortic® by Novartis) contain nystatin to treat fungal infec- Bag” or “Rally Pack.” An order for a tions or hydrocortisone or dexametha- “Banana Bag” is not a valid order. ◆ CRITERIA FOR USE CHANGED sone as anti-infl ammatories. Some “GI Cocktail” is another coined term Cefepime (Maxipime® by Elan)*** versions contain sucralfate instead that can lead to confusion. The typical Ciprofl oxacin of aluminum-magnesium hydroxide. (continued on page 3) (Cipro® and generics)*** There are even listed formulas that contain antibiotics like tetracycline ◆ Gatifl oxacin (Tequin® by Bristol or sulfamethoxazole-trimethoprim Myers Squibb)*** (Septra®). INSIDE THIS ISSUE ***Streamlining by the Anti-Infective Problems can arise when patients re- ◆ Restricted antibiotics in clinics Stewardship Program approved ceive a product different than what the prescriber intended. The patient could ◆ Annual index (continued on next page) have an allergy to one of the ingredi- Formulary update, from page 1 dehyde for atrial and ventricular septal estrogens), it was removed from the Clozapine is an atypical antipsy- defect (ASD & VSD) repairs. These data Formulary. chotic that was requested for addi- suggest that glutaraldehyde improves Magic Mouthwash is a mixture tion because of nonformulary use the durability of these repairs. of medications that has been used at Shands Vista. Clozapine has not However, there are signifi cant safety to treat mucositis, particularly in been listed in the Formulary bbecauseecause concerns with this product. Policies will patients receiving chemotherapy it previously was available only via be established for safe preparation, stor- for cancer. Magic Mouthwash has a limited-distribution program that age, labeling, handling in the operating been listed in the Formulary, and the prohibited it from being stocked in the room (OR), and disposal. The solution annual formulary review identifi ed hospital setting. Now it can be stocked. will be colored with fl uoroscein to avoid this listing as a potential safety risk. Published studies, systematic re- confusion with other clear . Prescribers may not be aware of its views, and evidence-based guidelines Glutaraldehyde 0.6% will only be deliv- constituents. justify the addition of clozapine based ered from the OR Pharmacy directly to The magic mouthwash formulation on its proven effectiveness. Because the staff performing the surgery. that has been used at Shands at UF of the potential to cause agranulocyto- Levofl oxacin is a third-generation consisted of 4 parts nystatin sus- sis in 1% of patients (or less), weekly fl uoroquinolone. It has been considered pension 100,000 units/mL, 3.5 parts white blood cell counts are required a restricted nonformulary drug. This diphenhydramine (Benadryl®) elixir, during the fi rst 6 months of treatment. category of drugs is being phased out and 1 part lidocaine (Xylocaine®) Bi-weekly monitoring is required for of the Formulary because it implies viscous 2%. There are other formula- the next 6 months, and monitoring is that a drug is reasonable and available tions of “Magic Mouthwash” used required monthly for patients treated for specifi c uses but is “nonformulary.” at other institutions (ie, containing longer than a year. If a patient’s white This is better described as a formulary aluminum-magnesium hydroxide blood cell count decreases below pre- agent that is restricted. Thus, the Anti- [Maalox®] and/or corticosteroids). established guidelines, they must stop Infective Subcommittee recommended This can be confusing. Patients may clozapine and not be rechallenged or that this designation be changed. This be allergic to 1 of the ingredients, risk death. does not alter the limited manner that which may not be appreciated based In addition to the risk of agranu- levofl oxacin will be used at Shands at on the labeling of the product. locytosis, clozapine has other poten- UF. A Cochrane evidence-based review tially serious adverse effects includ- Ondansetron is a selective sero- on the interventions for treating oral ing seizures, cardiomyopathy, and tonin antiemetic commonly used for mucositis in patients with cancer other cardiac and respiratory effects. chemotherapy-induced and post-opera- concluded that there was no evi- Clozapine’s other common adverse ef- tive nausea and vomiting. In January dence that Magic Mouthwash is ef- fects include weight gain, hyperglyce- 2000, ondansetron orally disintegrat- fective. The American Cancer Society mia (diabetes), sedation, hypotension, ing tablets (ODT) were added in the (ACS) guidelines for the prevention tachycardia, nausea, hyperlipidemia, Formulary. Ondansetron oral solid and treatment of oral mucositis state hypersalivation (especially at night), tablets were deleted and the policy of that there is no signifi cant evidence and sweating. dispensing the ODT for all oral orders of the effectiveness or tolerability of Hospital policy will assure appro- was adopted. This decision was made any mixture used for mucositis. priate monitoring of clozapine before because the ODT dosage form was Therefore, Magic Mouthwash was dispensing. In the hospital setting, more versatile and there was no dif- removed from the Formulary. Saline policies usually require weekly moni- ference in cost. The net effect was a rinse is recommended as an alter- toring so that the patient’s duration of decrease in inventory with a perceived native because there is published therapy does not need to be determined. increase in dosing fl exibility. The ODT evidence that saline mouthwash Current evidence-based guidelines could be used instead of an oral promotes healing and is equivalent to recommend clozapine for treatment- or, in some cases, in place of injectable other products used for mucositis. resistant schizophrenia, patients with ondansetron. Duloxetine is a selective serotonin/ schizophrenia and suicidal ideation Since that decision, there have been norepinephrine reuptake inhibitor or behavior, and possibly for patients 2 complaints. The ODT dosage form (SNRI), like venlafaxine. It has been with schizophrenia and assaultive is so light, that in some settings the approved for the treatment of major behavior. Because of the potential to tablets are prone to blowing away. For depressive disorder and painful cause severe adverse effects, clozap- example, in the Bone Marrow Unit, diabetic neuropathy. Off-label uses of ine is only used when patients have there have been reports of the ondan- duloxetine include fi bromyalgia and failed or cannot tolerate at least 2 setron ODT being blown away in the urinary incontinence. other therapies. laminar fl ow rooms. Other SSRI and SNRI medications The orally disintegrating clozapine Also, some patients cannot toler- in the Formulary include: escitalo- tablets (Fazaclo®) were designated ate the taste of ondansetron ODT. pram, fl uoxetine, paroxetine, ser- nonformulary and not available. They complain that the tablets are too traline, and venlafaxine. Duloxetine Glutaraldehyde is a chemical with sweet, and it exacerbates their nausea is 20 times more expensive than major uses based on its highly reac- and vomiting. These patients were fl uoxetine; 2 times more expensive tive properties that cross-link cellular switched to injectable ondansetron. than escitalopram, paroxetine, or ser- proteins. In the medical fi eld, glutaral- In order to address these problems, traline; and 1.5 times more expensive dehyde is used for cold sterilization of the oral solid was added in the than venlafaxine. surgical equipment and other instru- Formulary for use in patients who can- To evaluate the safety and effi cacy ments, like endoscopes. It is also used not tolerate the ODT. of duloxetine, several placebo-con- as a tissue fi xative. Estradiol valerate in oil is an intra- trolled trials have been conducted. Glutaraldehyde 0.6% solution was muscular dosage form of estrogen. It is a A comparative study of duloxetine evaluated for use in toughening tis- very old product that has not been used. versus paroxetine showed equal sue allografts used in cardiac surgery It has not been stocked in the Pharmacy effi cacy in the treatment of major de- and vessel repairs. There are pub- for many years, yet is still technically pressive disorder. Patients receiving lished retrospective series that dem- listed in the Formulary. Since there are duloxetine experienced less sexual onstrate the usefulness of glutaral- alternatives (eg, injectable conjugated (continued on next page) 2 Formulary update, from page 2 pound, mycophenolic acid. keting studies on this issue here at UF. dysfunction when compared to EC-MPS was developed with hopes CellCept® is available in a solid oral paroxetine and placebo. No other that slower and more distal absorption dosage form, an oral liquid dosage differences were signifi cant between from the would form, and an intravenous dosage the treatment groups. Venlafaxine decrease the occurrence of gastrointes- form. Myfortic® is available only in a and duloxetine have not been com- tinal adverse effects — most commonly, solid oral dosage form. pared, and no other head-to-head diarrhea. Unfortunately, this has not Myfortic® was not added in the trials have been conducted. been shown in clinical trials, as adverse Formulary, but will be available via A randomized, placebo-controlled effects were identical between the nonformulary request for patients clinical trial has compared duloxetine MMF and EC-MPS groups. who are already admitted on this to placebo to treat diabetic neuropa- When dosed using recommended product. At this time, there will be no thy. Treatment with duloxetine 60 doses for each medication, there ap- effort to switch patients from Myfor- mg 1 or 2 times daily improved mean pears to be no clinically signifi cant dif- tic® to CellCept®. pain scores from baseline. Adverse ference between these medications in The criteria for use for cefepime, events increased signifi cantly with pharmacokinetic, pharmacodynamic, or ciprofl oxacin, and gatifl oxacin were the increase in dose of duloxetine. clinical parameters. The only compara- revised to empower the Anti-Infec- Based on the lack of suffi cient data, tive pharmacokinetic study between tive Stewardship Program (AISP) to duloxetine remains nonformulary at these medications showed no signifi - streamline therapies. Once culture this time. cant difference in maximum concentra- results are known and/or infection is Myfortic® is an enteric-coated, tions (Cmax) or total drug exposure ruled out, the AISP is authorized to extended-release, solid oral dosage (AUC). EC-MPS was shown to have a streamline or discontinue cefepime, form of mycophenolic acid. Mycophe- longer time to maximum concentration ciprofl oxacin, or gatifl oxacin therapy. nolic acid inhibits lymphocyte purine (Tmax). This difference is not expected These actions will be based on synthesis by inhibiting the rate-limit- to contribute to any clinical outcomes. culture and sensitivity results and a ing enzyme in the de novo pathway No difference has been shown in thorough clinical review of the pa- for purine synthesis in lymphocytes. clinical outcomes (biopsy proven acute tient, which includes discussing the It is most often used in combination rejection, graft loss, death, or treat- patient with the appropriate service. with cyclosporine or tacrolimus and ment failure) or adverse effects at 6 and The AISP is also authorized to stop corticosteroids for the prevention 12 months with MMF and EC-MPS as therapy once a patient has completed of acute cellular rejection in organ studied in renal transplant patients in 2 an appropriate treatment course. transplantation. randomized controlled trials. If there is disagreement with a CellCept®, mycophenolate mofetil The hope for Myfortic® is that it will decision made by the AISP, there is (MMF), which is currently listed in have greater gastrointestinal tolerance an appeals process. If necessary, the the Formulary, is similar to Myfor- than mycophenolate mofetil. There are Chief of Staff would ultimately make tic®, enteric-coated mycophenolate anecdotal instances when patients have the decision about the appropriate- sodium (EC-MPS). MMF is a pro-drug been able to switch to Myfortic® and ness of the decision of the AISP. of mycophenolic acid, which the liver demonstrate better gastrointestinal tol- However, there are several interim hydrolyzes to form the active com- erance, and there are ongoing post-mar- steps before this would be necessary.

POLICIES AND PROCEDURES Medication safety, from page 1 Restricting anti-infectives in GI Cocktail includes liquid antacid (eg, Maalox®), viscous lidocaine, and an anticholinergic (Donnatol®, which “Hospital” clinics is a mixture of atropine, hyoscya- here are several clinics serviced Outpatient Bone Marrow mine, scopolamine and phenobarbi- T by the inpatient pharmacy services Transplant Clinic tal). The cocktail is given for chest and which are physically located in a pain to rule out gastrointestinal

“hospital” setting. These clinics have Burn Clinic problems versus a more serious caused some confusion regarding use complaint. Like many of these com- of restricted anti-infectives. It is estimated that this should be binations, the rational of the mixture The P&T Committee voted to restrict applicable only a few times each year. has been questioned. “GI Cocktail” anti-infective agents in these clinics Monday through Friday, Infectious is not a valid order. as is done in the inpatient units. The Diseases approval will be necessary. In the past, coined names have purpose of restriction is primarily to On holidays, Saturdays, and Sundays, been supported by pharmacies. prevent the development of resistant the anti-infective will be dispensed and Coined names for mixtures avoid organisms. As such, it makes sense then the case referred to the ID Service having many different possible for- to have the same restriction policies for follow-up on the next weekday. mulations, which enables the con- based on the physical location of these Approval of restricted anti-infectives coctions to be prepared in advance. clinics. Therefore, these restriction poli- for the BMT Clinic will be required on Although this is convenient, it may cies apply to the following clinics: weekends and holidays. not be safe. If mixtures are used, specifying the specifi c ingredients and their amounts could help avoid medication errors. Often a single ingredient can be used instead of these mixtures (eg, antacid instead of a GI Cocktail). Magic mouthwash mixtures will no longer be com- pounded. 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 19, No. 10 Nov./Dec. 2005 PO Box 100316 PERMIT NO. 94 Gainesville, FL 32610-0316 This publication is produced by the 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 2005. 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/professional/drugs/ bulletin.htm

2005 Annual index TOPIC ...... ISSUE/PAGE(S) TOPIC ...... ISSUE/PAGE(S) TOPIC ...... ISSUE/PAGE(S) Acamprosate ...... June/1–2 Estradiol Valerate ...... Nov-Dec/1–2 Nesiritide ...... July-August/1,3 Aluminum Hydroxide Capsules ...... October/1–2 Ethyl Chloride ...... March/1–2 ...... September/1,2 Anti-Infective Restriction in Clinics ....Nov-Dec/3 Factor VIIa ...... July-August/1,3 New Drugs 2004 ...... February/2,4 Arsenic Trioxide ...... July-August/1–2 Fibrin Sealant ...... May/1–2 Nonformulary Drug Presentations ...... June/4 Atomoxetine ...... March/1–2 Fluro-Ethyl® ...... March/1–2 NovoSeven® ...... July-August/1,3 Atovaquone Suspension ...... October/1–2 ...... July-August/1–2 OTC Brand Names & Errors ...... May/1 Banana Bag ...... Nov-Dec/1 Fluvoxamine ...... July-August/1–2 Ondansetron Tablets ...... Nov-Dec/1–2 Banned Abbreviations ...... January/1,4 Fenofi brate ...... June/1,3 Pain Ease® ...... July-August/1–2 ...... February/1 Fosphenytoin ...... January/1,3 Palifermin ...... May/1,3 Bevacizumab ...... June/1–2 Gatifl oxacin ...... Nov-Dec/1,3 Pantoprazole ...... January/1-3 Bismuth Subsalicylate ...... May/1–2 GI Cocktail ...... Nov-Dec/3 ...... July-August/3 Bivalirudin ...... April/1,3 Glimepiride ...... February/1–2 Pegvisomant ...... March/1,3 Bosentan ...... June/1–2 Glutaraldehyde ...... Nov-Dec/1–2 Percocet® ...... April/1 Butt Paste ...... Nov-Dec/1 Glycerin, Sterile, Anhydrous ...... March/1,3 ...... June/1,3 CA-MRSA ...... July-August/1,4 Hetastarch ...... March/1–2 Phosphorus Supplementation ...... October/1 Cefdinir ...... June/1-3 Imipenem-Cilastatin ...... March/1,3 Prescription Writing ...... September/3 Cefepime ...... April/3 Immune Globulin, Intravenous ...... March/1-3 P&T Committee Actions 2004-5 ...... September/1 ...... Nov-Dec/1,3 ...... October/1,3 Rasburicase ...... October/1–2 Cefotetan ...... January/1–2 ...... October/4 Revatio® ...... October/1–2 Cefoxitin ...... January/1–2 Infl uenza Vaccine ...... January/3–4 Secretin ...... March/1,3 Child-Pugh Score ...... June/1,3 Intravenous Proton Pump Sildenafi l ...... October/1–2 Chlorothiazide ...... May/1–2 Inhibitors ...... July-August/3 Sodium Phenylacetate-Sodium Cilostazol ...... January/1–2 Irbesartan ...... June/1,3 Benzoate ...... May/1–2 CiproDex® ...... January/1–2 Kaolin-Pectin ...... May/1–2 Sodium Tetradecyl Sulfate ...... October/1–2 Ciprofl oxacin ...... Nov-Dec/1,3 K-Phos® ...... October/1 Statin Standard Dose Times ...... September/2 Cipro® HC ...... January/1–2 Lansoprazole ...... January/1-3 Streptokinase ...... March/1,3 Clinical Practice Bulletin ...... March/1 Lanthanum Carbonate ...... July-August/1–2 Synercid® ...... March/1–2 Clofarabine ...... April/1–2 Levofl oxacin ...... Nov-Dec/1–2 Telithromycin ...... October/1–2 Clopidogrel ...... April/1,3 Magic Mouthwash ...... Nov-Dec/1,3 Trastuzumab ...... September/1–2 Clozapine ...... Nov-Dec/1–2 ...... Nov-Dec/1–2 Tricor® ...... June/1,3 Liquid ...... January/1–2 Medicaid Prescription Drug List ...September/3–4 Truvada® ...... January/1–2 Continuous Infusion Diuretics ...... February/3 Meningococcal Vaccine ...... April/1–2 ...... October/1–2 Controlled Substance Prescriptions .. October/3–4 Methadone ...... May/4 Tylox® ...... April/1 Crosseal® ...... May/1–2 Myfortic® ...... Nov-Dec/1,3 ...... June/1,3 DepoDur® ...... July-August/1-3 Naltrexone ...... June/1–2 Unasyn® ...... March/1–2 Dexmedetomidine ...... February/1,2 Natalizumab ...... April/1–2 Vancomycin ...... March/4 Diazoxide Injection ...... March/1,3 Neutra-Phos® ...... October/1 ...... May/3 4 Duloxetine ...... Nov-Dec/1-3 Ziprasidone ...... October/1–2