Volume 21, Number 10 November/December 2007 Drugs & Therapy B � U � L � L � E � T � I � N

POLICIES AND PROCEDURES FORMULARY UPDATE The Pharmacy and Therapeutics Standardized dosing times Committee met October 16, 2007. 2 drugs or dosage forms were added tandard medication administration first dose. For example, a twice daily in the Formulary, and 2 dosage S times have existed for many years. injectable antibiotic order is received at forms were deleted. 3 drugs or These times are in place to improve 1400. The first dose will be scheduled for dosage forms were designated efficiency and communication. The ad- 1500. Subsequent doses will be given at nonformulary and not available. The ministration times have been modified 0300 and 1500. use of 1 drug in the Formulary was recently based on feedback received There will be a series of educational restricted. from the Departments of Nursing and sessions scheduled with the medical and Pharmacy. When dosing times are not nursing staffs to go over the more subtle specified by the prescriber, the default implications of the new policy. These ◆ ADDED times in the table (see below) will be sessions will emphasize to prescribers Cinacalcet used. that “3 times a day” is not the same as (Sensipar® by Amgen) Sodium Chloride Tablets Standardized Dosing Times (generic) Interval Standard Times ◆ DELETED Daily 0900 2 times a day (BID) 0900, 2100 Lansoprazole Delayed-Release 3 times a day (TID) 0900, 1400, 2100 Suspension 0800, 1200, 1700 (52 Psych) (Prevacid® Packets by 4 times a day (QID) 0900, 1300, 1700, 2100 TAP Pharmaceuticals)* 5 times a day 0500, 0900, 1300, 1700, 2100 Tetracycline Syrup Every 3 hours 0000, 0300, 0600, 0900, 1200, 1500, 1800, 2100 (generic)* Every 4 hours 0100, 0500, 0900, 1300, 1700, 2100 *Nonformulary and not available Every 6 hours 0600, 1200, 1800, 2400 Every 8 hours 0800, 1600, 2400 ◆ NONFORMULARY AND Every 12 hours 0900, 2100 NOT AVAILABLE Every 24 hours Time will default to hour profiled (ie, 1st order processed) Lubiprostone Bedtime 2100 (Amitiza® by Takeda With meals 0800, 1200, 1700 Pharmaceuticals) With meals and at bedtime 0800, 1200, 1700, 2100 Injectable antibiotics Times determined by the time the 1st dose is processed ◆ CRITERIA-FOR-USE CHANGES Corticotropin Repository There are several medications that “every 8 hours.” For oral drugs, every- Injection (Acthar® Gel by have unique specified dosing times: to 8-hour dosing requires that patients be Questor Pharmaceuticals)† allow laboratory values to be evaluated awakened to receive their dose. Waking †Restricted to approval by Pediatric before the dose is given (ie, warfarin , the patient may or may not be neces- Neurology for infantile spasms epoetin, darbepoetin, and filgrastim at sary, depending on the medication. 1800); to avoid meals (ie, oral fluoro- For more information on standardized quinolones at 0600 and 1600 [meals dosing times or to schedule an inservice Cinacalcet was evaluated for are generally given at 0800, 1200, and on this topic, contact Dr. Erin Jones in possible addition in the Formulary 1700]); convention (ie, cyclosporine at the Department of Pharmacy Services at because of high-volume nonformu- 0800 and 2000); for patient convenience 265-0404. lary use. Cinacalcet is an oral calci- (ie, furosemide at 0900 and 1800); and, mimetic agent that was approved to improve efficacy (ie, statins at bed- by the FDA in March 2004. It is the ◆ time). only agent in its therapeutic class. Because injectable antibiotics should INSIDE THIS ISSUE Cinacalcet has labeled indications be started as soon as possible and for use in the treatment of second- ◆ prolonged intervals could affect efficacy, Medical foods? ary hyperparathyroidism in patients the dosage time for injectable antibiot- ◆ Annual index (continued on next page) ics will be determined by the time of the Formulary update, from page 1 The new enteral feeding system used has an FDA-labeled indication for the with chronic kidney disease on dialysis by Dietary Services does not allow the treatment of chronic idiopathic consti- and for the treatment of hypercalcemia addition of specific electrolytes. Extra pation. The labeled dose is 1 capsule in patients with parathyroid carcinoma. sodium chloride must be administered (24 mcg) twice daily with meals. The Chronic kidney disease is associated separately. This is usually done using drug has not been specifically stud- with hyperphosphatemia, hypocalce- sodium chloride 4 mEq/mL injection in ied in patients with hepatic or renal mia, and increased stimulation of the an oral syringe. However, adult and impairment, but the need for dos- parathyroid gland. These alterations older pediatric patients who can take age adjustments is unlikely as it has lead to secondary hyperparathyroid- oral solids can be supplemented with minimal systemic availability. Safety ism, a progressive condition that 1-gram sodium chloride tablets (ie, de- and efficacy have not been established eventually results in bone disease livering 17.2 mEq of sodium per tablet). in children or adolescents. A lower and calcification of vascular and soft Prevacid® for Delayed-Release Oral strength of lubiprostone (ie, 8 mcg) to tissues. Suspension Packets will no longer be treat irritable bowel syndrome with Cinacalcet acts on the calcium- marketed by TAP Pharmaceuticals. This constipation is currently under review sensing receptor on the surface of the product is not used much; other dosage by the FDA. chief cell in the parathyroid gland. The forms are more popular. The packets There are no head-to-head studies calcium-sensing receptor is the princi- were deleted from the Formulary and comparing lubiprostone to other agents pal regulator of parathyroid hormone designated nonformulary and not avail- used to treat chronic constipation (ie, (PTH) secretion. By mimicking calcium, able. bulk-forming fiber products or stool cinacalcet increases the sensitivity of Lansoprazole suspension compound- softeners). The approval of lubipros- the calcium-sensing receptor to extra- ed using sodium bicarbonate is a better tone was primarily based on 2 random- cellular calcium and lowers PTH levels. alternative for administering lansopra- ized, double-blind, placebo-controlled, Decreased serum calcium is associated zole down a feeding tube. Prevacid® phase 3 trials that showed moder- with reduction in PTH. After 1 week of Oral Suspension Packets produced a ate improvements in weekly bowel therapy, reduction in serum calcium is thick suspension because it contained movements (ie, an absolute increase seen and maintained. xanthan gum to increase viscosity. This of approximately 2 bowel movements Managing patients, according to the thick suspension often clogged feeding per week [approximately 3 vs 5]). Also, National Kidney Foundation’s Kidney tubes, especially small-bore feeding only approximately 60% of patients Disease Outcomes Quality Initiative (K/ tubes. had a spontaneous bowel movement in DOQI) guidelines on bone metabolism Prevacid® SoluTabs® have a pleas- the first 24 hours of treatment. and disease in chronic kidney disease, ant taste and can be used to administer The most commonly reported ad- can be challenging. Traditional thera- lansoprazole orally in small children who verse effect during clinical trials was pies for stage 5 chronic kidney disease cannot swallow capsules. The SoluTabs® nausea. The incidence of nausea is include phosphate-binders and vitamin can also be dissolved in a small amount dose-related; 8% of patients discontin- D sterols and can be associated with of water and administered down a feed- ued treatment during trials due to nau- hypercalcemia. ing tube. The granules in the SoluTabs® sea. Other common side effects during Evidence from randomized, placebo- do not clump or stick to the feeding tube. trials included diarrhea, headache, and controlled trials in dialysis patients Tetracycline syrup has been discon- abdominal pain or distension. shows that cinacalcet is effective in tinued by its manufacturer. There is no Chronic constipation is primarily reducing intact PTH while also reduc- alternative source. After consulting with treated on an outpatient basis. There ing serum calcium, phosphorus, and the Infectious Diseases Subcommittee, are various low-cost formulary op- calcium-phosphorus product. At the there appears to be no need to recom- tions available for acute treatment of start of these studies, patients had mend an alternative agent. Tetracycline constipation (eg, senna), as well as elevated PTH in spite of treatment syrup was designated nonformulary and fiber products and stool softeners for with phosphate binders and/or vitamin not available. possible prevention. Patients admit- D sterols. At this time, a large prospec- Lubiprostone was evaluated for pos- ted who are already taking lubipros- tive, randomized, placebo-controlled sible addition in the Formulary based on tone may take their own supply or be trial is being conducted to determine if requests for use and potential for inap- treated with other formulary agents cinacalcet reduces the risk of mortality propriate off-label use. for constipation during hospitaliza- or cardiovascular events in hemodialy- Lubiprostone is a member of a new tion. Additionally, discontinuation sis patients. class of bicyclic fatty acids prostaglan- of lubiprostone does not result in a

The most common adverse events din E1 derivatives known as prostones. rebound effect and, in fact, shows a associated with cinacalcet use are It increases intestinal fluid secretion via sustained response 3 weeks after stop- nausea and vomiting. Cinacalcet may a novel mechanism of action by specifi- ping the drug. Therefore, lubiprostone be associated with increased risk of cally activating type 2 chloride channels. was designated nonformulary and not seizures, hypocalcemia, and adynamic The secretions subsequently soften available. bone disease. Drug interactions in- the stool, increase intestinal motility, Acthar® Gel remains listed in the volving the cytochrome P450 enzyme promote spontaneous bowel move- Formulary; however, it is now re- system are possible with concomitant ments, and relieve signs and symptoms stricted to prior approval by Pediatric cinacalcet therapy. Increased monitor- of constipation. Neurology for use in the treatment of ing of serum calcium and PTH may Lubiprostone is administered infantile spasms. Product will not be be necessary to manage the risks of orally and has low systemic availability. stocked for use in the hospital and severe adverse events. Plasma concentrations are below the will be obtained only for use in Compared with other oral medica- level of detection; there are no known patients who have been approved tions, cinacalcet is quite expensive. drug interactions. A clinically meaning- for use in the product’s restricted- Based on typical dosages, it will cost ful effect usually occurs within 1 week distribution program. approximately $1000 per month. of administration, and tolerance to use The changes in the formulary status Sodium chloride tablets were has not been observed during clinical of Acthar® Gel are the result of Questor deleted from the Formulary during a trials. Additionally, a sustained response Pharmaceuticals’ recent announce- time of shortage. The shortage has has been shown 3 weeks after stopping ment that it increased the cost of a been resolved, and there is now a need therapy. 5-mL multi-dose vial (80 units/mL) to re-add this dosage form back in the Lubiprostone, which was approved by from its previous price of about $1,500 Formulary. the FDA in January 2006, currently only (continued on next page) 2 Formulary update, from page 2 Oral prednisone (20-60 mg per day hormone secretion, and adipokinetic per vial to $23,000 per vial! This is tapered over 10 days) is an option for effects are also similar. more than a 15-fold increase. The patients who can take oral medications. According to Cortrosyn® labeling, 25 manufacturer states this price is in line Intramuscular or intravenous methyl- units of corticotropin is pharmacologi- with other drugs that are used to treat prednisolone (100 mg per day with cally equivalent to 0.25 mg cosyntro- rare disorders. taper) is another inexpensive alterna- pin based on the level of stimulation Shands at UF has been a relatively tive. There are also data supporting the on the adrenal cortex. Based on this heavy user of Acthar® Gel. Without the use of a 60-mg dose of intramuscular tri- conversion, 0.4 to 0.8 mg of cosyntro- current restrictions, there could have amcinolone acetonide for the treatment pin would be an equivalent dose for been an increase in pharmaceutical of gout, but this is nearly 17-times more treating gout (ie, equal to a 40 to 80 expenditures of $1.4 million. expensive than methylprednisolone. unit dose of Acthar® Gel). This treat- A review of the last year’s Acthar® Cosyntropin (Cortrosyn®), a synthetic ment is as much as 300 times more Gel use showed that most was being form of adrenocorticotropic hormone expensive than methylprednisolone. used for the treatment of acute gout. (ACTH) that contains the biologically ac- Acthar® Gel is about 15 times more There are multiple alternative agents tive amino acid portion of ACTH, can be expensive than cosyntropin. A table that can be used to treat an acute used as an alternative to Acthar® Gel for with drug, dosage, and cost compari- exacerbation of gout. Nonsteroidal the treatment of gout. Cosyntropin has sons of drugs used for the treatment anti-inflammatory agents (NSAIDs) less antigenicity than natural ACTH. of acute gout can be found on the and colchicine are commonly used. Studies showing benefit from ACTH intranet at http://intranet.shands.org/ However, patients who cannot tolerate in gout did not use synthetic ACTH. pharm/Acute_Gout_Rx.pdf. an NSAID or colchicine can be treated However, cosyntropin does stimulate Acthar® Gel has also been used to with corticosteroids. Intra-articular the adrenal cortex maximally and to the treat multiple sclerosis exacerbations. steroids are an option when 1 or fewer same extent as an equivalent dose of There are other alternatives (eg, joints are involved. There are several natural ACTH. Additionally, the common methylprednisolone) that are other oral and parenteral alternatives extra-adrenal effects including increased preferable in this condition. to Acthar® Gel. melanotropic activity, increased growth

NEWS Medical foods: Drug, dietary supplement, food, or other? hat is a medical food? Is it a claims for dietary supplements. Manu- foods through establishment inspec- Wdrug? Is it a dietary supplement? facturers can make disease-specific tions, (2) collect domestic and im- Is it a food? Or maybe it’s something statements for these products. port surveillance samples of medical else entirely? If you answered “some- Medical foods are foods, however, foods for nutrient and microbiological thing else entirely,” you are correct. and are at least required to have a analyses, and (3) take action when sig- The term “medical food” is officially certain amount of labeling. This must nificant violations of the Federal Food, defined by the FDA in a section of include: a statement of identity; an ac- Drug and Cosmetic Act (or related the Orphan Drug Act Amendments of curate statement of the net quantity of regulations) are found. 1988. The term “medical food” does contents; name and place of business What medical foods are available? not simply apply to all foods fed to sick of the manufacturer, packer, or distribu- The prototypical example of a medical patients. A medical food is “a food tor; and a complete list of ingredients. food is the phenylalanine-free nutrition- which is formulated to be consumed Also the Food Allergen Labeling and al supplement (PhenylAid®) for patients or administered enterally under the Consumer Protection Act (FALCPA) re- with phenylketonuria (PKU). Other supervision of a physician and which is quire that medical foods include on the examples of products that claim to be intended for the specific dietary man- label the food source name of any major medical foods include: L-methylfolate agement of a disease or condition for allergens (ie, peanuts, eggs, shellfish). (Deplin®) for depression; flavocoxid which distinctive nutritional require- Furthermore, medical foods must com- (Limbrel®) for osteoarthritis; lactic ments, based on recognized scientific ply with all applicable requirements for acid bacteria (VSL#3®) for ulcerative principles, are established by medical the manufacture of foods in general, colitis, IBS, or ileal pouch; Complex evaluation.”A couple key points are: such as the Current Good Manufactur- MSUD® Drink Mix for branched-chain physician supervision, taken orally, and ing Practices regulations. alpha-keto acid dehydrogenase taken for a specific nutritional need for So what are the implications of the deficiency (Maple Syrup Urine Dis- a certain condition. A medical food is lax regulation of medical foods? Due ease); UltraClear® for chronic fatigue NOT required to be prescription only; to lack of regulatory control, the FDA syndrome; Estrium® for symptoms over-the-counter products can be used historically has paid little attention to related to the “female hormone cycle”; under medical supervision. medical foods. This created an environ- UltraGycemX® for conditions associ- So how are medical foods regulated? ment wherein manufacturers — taking ated with type 2 diabetes; and Trama- Since they fall into a unique class they advantage of an opportunity not to Cal® Liquid for metabolically stressed are regulated differently than both have to get FDA approval — started patients (eg, burn patients). Many of drugs and dietary supplements. to market a variety of food products as these products have a Web page if you Medical foods do NOT have to medical foods, regardless if they qualify are interested in additional informa- undergo pre-marketing review or be as such. tion; however, some of the claims made approved by the FDA; individual medi- Based on possible safety concerns, for these products are not backed by cal food products do not have to be the FDA has recently developed a Com- the standards of evidence that we registered with the FDA. Additionally, pliance Program specifically for would expect for drugs. medical foods are exempted from the medical foods. This program enables By Russell McKelvey, PharmD labeling requirements for health claims FDA inspectors to do the following: References and nutrient content claims under the (1) obtain information regarding the Guidance for Industry: Frequently Asked Questions About Nutrition Labeling and Education Act manufacturing/control processes and Medical Foods. U.S. Department of Health and Human Ser- vices Food and Drug Administration Center for Food Safety of 1990. As a result, medical foods are quality assurance programs employed and Applied Nutrition. May 2007. Accessible at: http://www. not limited to the “structure/function” by domestic manufacturers of medical cfsan.fda.gov/~dms/medfguid.html. 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 21, No. 10 Nov./Dec. 2007 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 2007. 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

2007 Annual index TOPIC...... ISSUE/PAGE(S) TOPIC...... ISSUE/PAGE(S) TOPIC...... ISSUE/PAGE(S) Acthar® Gel...... September/4 Epoetin-Darbepoetin Interchange...... January/1 Mometasone-Fluticasone Nasal Spray ...... November–December/1–3 ...... September/1,3 Interchange...... January/1–2 Albumin...... February/3 Erythropoiesis-Stimulating Agent Morphine Extended-Release...... February/1–2 ...... May/1–2 Protocol...... September/1 MS-Contin®-Oramorph® Aminoglutethimide...... April/1–2 Esomeprazole...... July–August/1–2 Interchange...... February/1–2 Amprenavir...... February/1–2 Fluticasone-Mometasone Nasal Mycophenolate...... April/1–2 Anidulafungin...... January/1–2 Spray Interchange...... January/1–2 New Drugs 2006...... February/1,4 Antihemophilic Factor...... September/1–3 Fluvastatin...... April/1–2 Off-Label Promotion...... March/1–2 Antihemophilic Factor, Porcine...... September/1–3 Gammagard® S/D...... February/1–2 Olanzapine...... June/1–2 Antimicrobial Management...... April/3 Generic Drugs...... May/1,3 Oramorph®-MS-Contin® Aripiprazole...... June/1–2 Gonadorelin...... September/1,3 Interchange...... February/1–2 Benazepril-Lisinopril Halothane...... January/1–2 Pegfilgrastim...... April/1 Interchange...... February/1–2 Heparin Levels...... April/1,4 Pergolide...... May/1–2 Benzylpenicilloyl-Polylysine Histamine Skin Test...... February/1–2 Pioglitazone...... July–August/1–2 Skin Test...... February/1–2 Hydroxocobalamin...... September/1–2 Pneumococcal Vaccine...... July–August/1 Buprenorphine...... September/1–2 Hydroxyzine Syrup...... July–August/1–2 Posaconazole...... January/1–2 Buprenorphine-Naloxone...... September/1–2 Hyoscyamine...... June/1–2 Potassium Chloride...... June/1,3 Caffeine Tablets...... September/1–2 Imipenem...... September/1,3 Pravastatin...... April/1–2 Calcium Chloride...... July–August/4 Immune Globulin, Intravenous...... February/1–3 Promethazine...... January/3–4 Calcium Gluconate...... July–August/4 Infliximab...... July–August/1,3 Propoxyphene...... September/1,3 Cefixime...... September/1–2 Insulin Aspart-Insulin Aspart Quinine...... January/1,3 Ceftriaxone...... May/1,3 Protamine...... September/1–2 Ranolazine...... April/1–2 Charity Care Formulary...... May/1 Insulin Detemir...... March/1–2 Rosuvastatin...... January/1–3 Cinacalcet...... November–December/1–2 Insulin Glargine...... September/1–2 ...... April/1–2 Cockroft-Gault Equation...... March/3 Insulin Lispro-Insulin Lispro Simvastatin...... April/1–2 Conivaptan...... July–August/1–2 Protamine...... September/1–2 Sodium Chloride Cyanide Antidote Kit...... September/1,3 Iron Sucrose Injection...... June/1–2 Tablets...... November–December/1–2 Cyclosporine, Generic...... March/1 Itraconazole...... September/1,3 Sodium Phosphate...... July–August/4 Cyclosporine, Gengraf®...... June/1–3 Ketorolac...... April/1–2 Standardized Dosing Cyclosporine, Neoral®...... June/1–3 Lansoprazole...... May/1,3 Times...... November–December/1 Darbepoetin...... May/1,3 Lansoprazole Suspension Standardized IV Concentrations...... May/4 ...... June/1 Packets...... November–December/1–2 Tegaserod...... May/1–2 Darbepoetin-Epoetin Interchange...... January/1 Levetiracetam...... February/1–2 Teniposide...... April/1–2 ...... September/1,3 Lidocaine Patches...... May/1–2 Tetanus-Diphtheria-Pertussis Decitabine...... March/1–2 Lisinopril-Benazepril Interchange.... February/1–2 Vaccine...... January/1–2 Desonide Ointment...... January/1–2 Lovastatin...... April/1–2 ...... July–August/1,3 Disposal of Drugs...... April/3 Lubiprostone...... November–December/1–2 Tetracycline Syrup...... November–December/1–2 Doctoring Orders...... June/3 MDRD Equation...... March/3 Therapeutic Interchange...... February/3 Duloxetine...... March/1–2 Medical Foods...... November–December/3 Tranexamic Acid...... April 1–2 Enteral Feeding Tubes, Meningococcal Vaccine...... March/1–2. Vancomycin...... July–August/3 Drug Administration...... March/3–4 ...... June/3–4 Voriconazole...... September/1,3 Epoetin...... May/1,3 Meropenem...... September/1,3 Zalcitabine...... July–August/1–2 4 ...... June/1 Micafungin...... January/1–2 Ziprasidone...... June/1–2