Managing Drug Shortages: Seven Years' Experience at One Health

REPORTS Managing drug shortages

REPORTS

Managing drug shortages: Seven years’ experience at one health system

ERIN R. FOX AND LINDA S. TYLER rug shortages have substantially affected patient care over the Abstract: A health system’s experience in therapeutic categories were central ner- past few years. While shortages monitoring drug shortages since 1996 vous system agents (24%) and serums, D within the organization and since 2001 on a toxoids, and vaccines (17%). Of the 119 have no single cause, manufacturing national level is described. shortages in 2001, 70 (59%) were still on- problems, regulatory actions, busi- Since January 1996, the Drug Informa- going as of the end of June 2002. The most ness decisions, and inventory prac- tion Service (DIS) at the University of Utah common potential safety problems were tices all contribute to the phenome- Hospitals and Clinics (UUHSC) has system- that clinicians might be unfamiliar with the non. Determining the true frequency atically prepared written bulletins to affect- alternative agent (54%) and that the alter- of drug shortages is difficult, in part ed practitioners when drug shortages native’s dosage requirement was different because “drug shortage” means dif- occurred. The DIS began providing infor- (50%). Over half of the shortages were cost ferent things depending on one’s mation on a national level to the American neutral, but the assessment did not include Society of Health-System Pharmacists in substantial potential indirect costs. perspective. Most health care organi- January 2001. Detailed information on drug shortages zations consider a drug shortage to A total of 224 drug shortages were collected by a health system’s drug infor- be a supply issue that affects how the tracked from January 1996 to June 2002. All mation service since 1996 indicated a trend pharmacy prepares a product or in- shortages at UUHSC were also national toward more frequent shortages. fluences patient care when prescrib- shortages, but only about two thirds of na- ers must choose an alternative thera- tional shortages also affected UUHSC. The Index terms: Central nervous system py. Manufacturers may consider a most common reasons for shortages were drugs; Costs; Dosage; Drug distribution; manufacturing problems (28%) and prod- Drug information centers; Manufacturing; drug shortage to be a problem with uct discontinuation (20%). The most Serums; Toxoids; Vaccines raw-material availability or a prob- frequently represented pharmacologic– Am J Health-Syst Pharm. 2003; 60:245-53 lem in manufacturing resulting in sustained unavailability of certain products. Wholesalers may define a that pharmacies face regularly. Fluc- frequency of industry back orders to shortage as difficulty obtaining a tuations in supply and demand pharmacies was 7%; by December product, regardless of the reason or among manufacturers, wholesalers, 2001, the rate had increased to 23% the duration. Often no distinction is and health care organizations occur (Streck RJ, Healthcare Distribution made between a back order and a daily but do not always constitute a Management Association Survey Re- shortage. For this article, we define a drug shortage. Pharmacies are adept search Program, personal communi- drug shortage from the perspective at dealing with these temporary sup- cation, 2002 Jan 31). of the health care organization. This ply issues. However, like drug short- Starting in 1996, the University of definition does not include the tem- ages, these fluctuations in supply Utah Drug Information Service porary back orders and supply issues have increased. In 2000, the average (DIS) systematically prepared written

ERIN R. FOX, PHARM.D., is Assistant Professor (Clinical) of Pharmacy The Drug Information Service at University of Utah Hospitals and Practice and Drug Information Specialist and LINDA S. TYLER, Clinics develops and provides information on drug shortages to the PHARM.D., FASHP, is Professor (Clinical) of Pharmacy Practice and American Society of Health-System Pharmacists under a grant from Pharmacy Manager, Drug Information Service, University of Utah Novation. This information is available to the public at www. Hospitals and Clinics, Salt Lake City. ashp.org/shortage. Address correspondence to Dr. Fox at the Department of Pharma- cy Services, A-050, University of Utah Hospitals and Clinics, 50 N. Copyright © 2003, American Society of Health-System Pharma- Medical Drive, Salt Lake City, UT 84132 ([email protected]). cists, Inc. All rights reserved. 1079-2082/03/0201-0245$06.00.

Am J Health-Syst Pharm—Vol 60 Feb 1, 2003 245 REPORTS Managing drug shortages memos for the affected practitioners at management strategies for the health group purchasing organization, University of Utah Hospitals and care practitioners likely to be affect- Novation. FDA’s “Orange Book” Clinics (UUHSC) when shortages ed. Shortages were identified by the (Approved Drug Products with Thera- occurred. The DIS had long involved buying staff in the department and peutic Equivalence Evaluations) and physicians in the management of sometimes by pharmacists. Once a National Drug Code Directory and in- drug shortages. It was important to shortage was brought to the atten- formation from our wholesaler were inform prescribers of drug shortages tion of the DIS, the staff reviewed the used to determine the manufacturers as soon as possible and to involve purchasing status with the buyers, and national drug codes of the prod- them in decisions when drug prod- obtained information from the ucts in question. The process of ucts needed to be allocated within wholesaler, contacted the manufac- contacting the manufacturers was the organization. This philosophy turer, and assessed our inventory. standardized. The customer service was developed in the late 1980s. Phy- Given that information, the staff as- department of each manufacturer sicians who understood that the sessed the potential for an impact on was contacted about the availability pharmacy had made every effort to patient care. If a potential existed, a of the drug product in question. If obtain a product were more likely to memo was prepared that outlined the customer service department work constructively with pharmacy the situation, how patient care might could not provide a reason for the to find appropriate solutions for be affected, and the clinical options shortage, the manufacturer’s medical managing shortages and preventing a practitioners should consider during information department and local negative impact on the patient. On the shortage. Every attempt was sales representatives were contacted. the other hand, prescribers who were made to involve prescribers and Manufacturers were contacted inter- surprised by supply problems were pharmacists with direct patient care mittently during the shortage until often unprepared to care for patients responsibilities in any decisions re- the product was widely available. in the context of a shortage. garding the allocation of a product in Shortage data from 1996 to 1999 Drug shortages came to the atten- short supply. The pharmacy and were collected from past UUHSC bul- tion of the American Society of therapeutics committee was respon- letins. Also, beginning in January Health-System Pharmacists (ASHP) sible for approving allocation proce- 2001, the data for shortages were en- beginning in the late 1990s.1-4 Mem- dures. Bulletins explaining why a tered into a spreadsheet (Excel, Mi- bers were informing ASHP about the shortage was occurring, the expected crosoft Corp., Redmond, WA). This dramatic impact that shortages were duration, and alternative agents or was necessary not only because of the having on their institutions. Two no- management strategies were distrib- dramatic increase in the number of table shortages during this time in- uted to prescribers, nursing manag- supply problems but also for tracking volved immune globulins and uroki- ers, and all pharmacy personnel. the shortages more consistently and nase. In response, ASHP prepared Originally, these bulletins were reliably. Information collected from guidelines on managing drug product printed and distributed manually. our bulletins and spreadsheets includ- shortages and developed a resource Later, the information was e-mailed ed the number of shortages docu- center on its Web site. to targeted practitioners. mented each year and, for each short- This article summarizes our expe- ASHP launched its Drug Product age, the product involved, the reason rience in monitoring drug shortages Shortages Management Resource for the shortage, whether the shortage since January 1996 within our organ- Center (www.ashp.org/shortage) in affected just the pharmacists or other ization and since January 2001 on a January 2001. The UUHSC DIS be- health care professionals also, the ther- national level. gan to provide clinical content for apeutic category, the level of impact on this Web site under a contract with patient care, and a safety and cost as- Methods ASHP and Novation. For this ar- sessment. Data on the impact on care, In January 1996, the UUHSC DIS rangement, the internal bulletins of safety, and cost that were not assessed began tracking drug shortages— UUHSC were adapted to a national at the time of the shortage were deter- supply problems that could affect pa- audience and potential shortages mined from the descriptions in our tient care or how the pharmacy were researched regardless of wheth- bulletins for shortages prior to 2001. would prepare the drug. Back orders er they would affect our institution. The durations of shortages were were not considered shortages unless The resulting descriptions of short- not assessed, as this information was they were of a duration sufficient to ages were posted as Drug Product not available before 2001. The DIS affect care. Enough outages had oc- Shortage Bulletins on the ASHP Web considers a drug shortage to be re- curred from time to time that a sys- site. Shortages were also identified by solved when the product is widely tem was in place for researching a broader audience, including those available to all purchasers from the potential shortages and preparing contacting ASHP, and through our manufacturers. Because manufactur-

246 Am J Health-Syst Pharm—Vol 60 Feb 1, 2003 REPORTS Managing drug shortages ers’ warehouses may differ in distri- products represented 156 (69%) of diphtheria toxoids adsorbed, be- bution methods, shortages may last all 224 shortages. tamethasone, dexamethasone, hepa- longer in some parts of the nation The most common reason for titis B vaccine, nimodipine, and than in others. Likewise, institutions shortages was manufacturing diffi- pneumococcal 7-valent conjugate that order directly from a manufac- culties (62 shortages [28%]), fol- vaccine). Our hospital used the same turer may be able to obtain the prod- lowed by product discontinuation drugs with alternative vial sizes or uct sooner than hospitals that solely for any reason or a business decision strengths in 10 cases (4%) (involving use wholesalers. The exact duration to stop making the product (45 diphenhydramine, doxorubicin, of a shortage is difficult to determine [20%]), a supply-and-demand im- methylprednisolone, heparin, gen- because of these variations. balance or a restriction on distribution tamicin, and dobutamine). Two (22 [10%]), a raw-material shortage shortages (1%) were managed by Results (19 [8%]), and regulatory problems therapeutic interchange (ranitidine Table 1 lists the drug shortages (16 [7%]). The reason for 59 (26%) of syrup and dexamethasone). tracked by the DIS from January the shortages was unknown. Table 3 shows the American Hospi- 1996 through June 2002. Each short- Each shortage was categorized as tal Formulary Service pharmacologic– age was associated with one product. to its impact on UUHSC and the rec- therapeutic classifications of the prod- Figure 1 shows the number of short- ommendations that we made nation- ucts involved in the shortages. The ages experienced at UUHSC from ally via the ASHP Drug Product categories with the greatest represen- January 1996 to June 2002 and the Shortages Management Resource tation were central nervous system number of shortages reported na- Center (Table 2). The category with agents (15%), serums, toxoids, and tionally from January 2001 to June the highest frequency of shortages vaccines (10%), hormones (10%), 2002. The DIS tracked a total of 224 was “no product available, but alter- antiinfectives (14%), and autonomic shortages during the 1996–2002 peri- natives recommended” (68 shortag- agents (9%). od, 170 of them affecting UUHSC. All es [30%]). “No product available Data assessing the duration of each shortages at UUHSC were also nation- and no alternatives recommended” shortage were not available. However, al shortages, but not all national short- accounted for 28 shortages (13%). the number of continuing and re- ages were experienced at our institu- Products were discontinued in 29 solved shortages could be assessed for tion. Of the 157 national shortages cases (13%). Organizational meas- the period from January 2001 to June from January 2001 through June ures were used to manage several 2002. Of the 119 shortages in 2001, 2002, 108 (69%) affected UUHSC. shortages. The available stock of 70 (59%) were still ongoing as of Reasons national shortages may not drug was rationed at UUHSC ac- June 30, 2002. Thirty-eight shortages have affected UUHSC included re- cording to pharmacy and therapeu- were identified from January 2002 to gional variability, infrequent use, and tic committee criteria in 7 cases (3%) June 2002, and 27 (71%) continued nonformulary status. Parenteral drug (immune globulin, tetanus and as of June 30, 2002. Each shortage experienced at Figure 1. Number of drug product shortages at the University of Utah Hospitals and Clinics UUHSC from January 1, 2001, to (gray bars) and nationally (black bars). National tracking began in January 2001. June 30, 2002, was also assessed for its potential impact on patient safety 140 (Table 4). This assessment involved a combination of our own assessments 120 and safety assessments developed by the Veterans Affairs National Center 100 for Patient Safety.5 The most common potential safety problems were 80 that clinicians might be unfamiliar with the alternative agent (59 short- 60 ages [54%]) and that the dosage re-

No. Shortages No. 40 quirement of the alternative agent was different from that of the prod- 20 uct in short supply (54 [50%]). Actu- al patient harm was not assessed. 0 All shortages were assessed for 1996 1997 1998 1999 2000 2001 June 2002 their potential impact on drug costs Year to the organization. Twenty-nine

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Table 1. Drug Product Shortages Tracked by University of Utah Hospitals and Clinics, January 1996 to June 2002 Reason for Year Shortage Product Shortage Began Acetazolamide sodium injection (Diomox) Unknown 2002 Albumin human Discontinuation or business decision 1997 Albuterol sulfate repeat-action tablets Business decision 2001 Alosetron hydrochloride tablets Discontinuation or business decision 2000 Aminocaproic acid syrup Unknown 2001 Amiodarone injection Unknown 2002 Amiodarone tablets Unknown 2002 Antiinhibitor coagulant complex injection Manufacturing problems 2001 Antivenin (Crotalidae) polyvalent injection Business decision 2001 Aprotinin injection Unknown 2001 Asparaginase injection Unknown 2001 Aspirin suppositories Discontinuation or business decision 2000 Atenolol injection Manufacturing problems 1998 Atovaquone tablets Discontinuation or business decision 1997 Atropine sulfate 0.5% ophthalmic solution Discontinuation or business decision 2002 Bacitracin injection Manufacturing problems 2001 Benztropine injection Manufacturing problems 2001 Betamethasone sodium phosphate–betamethasone acetate injection Manufacturing problems 2000 Botulinum toxin type A injection Regulatory problems 1997 Bretylium tosylate injection Raw-material shortage 1999 Budesonide respules Supply and demand 2002 Bumetanide injection Supply and demand 2002 Butalbital–acetaminophen or butalbital–aspirin–caffeine tablets Unknown 2001 Calcitriol capsules Raw-material shortage 2001 Calcium chloride prefilled syringes Unknown 2001 Carboprost injection Manufacturing problems 2002 Caspofungin acetate injection Manufacturing problems 2001 Cefotaxime sodium injection Unknown 2001 Cerivastatin sodium tablets Discontinuation or business decision 2001 Chloral hydrate suppositories Discontinuation or business decision 1996 Chlordiazepoxide injection Manufacturing problems 2001 Chlorothiazide injection Unknown 2001 Ciprofloxacin hydrochloride tablets Unknown 2001 Ciprofloxacin injection Supply and demand 1999 Cisapride tablets, oral suspension Discontinuation or business decision 2000 Cisatracurium besylate injection Manufacturing problems 2001 Clotrimazole vaginal tablets Discontinuation or business decision 2000 Cocaine topical solution Unknown 2000 Conjugated estrogens tablets Manufacturing problems 2001 Conjugated estrogens injection Unknown 2001 Corticotropin injection Discontinuation or business decision 1997 Corticotropin injection Raw-material shortage 1999 Cosyntropin injection Unknown 2001 Cromolyn sodium oral concentrate Manufacturing problems 2002 Cyclopentolate–phenylephrine ophthalmic solution Unknown 1998 Danaparoid sodium injection Supply and demand 2001 Dexamethasone sodium phosphate injection Manufacturing problems 2001 Dexfenfluramine hydrochloride tablets Discontinuation or business decision 1997 Dexrazoxane injection Manufacturing problems 2001 Diatrizoate sodium injection Manufacturing problems 2001 Diazepam injection Business decision 2001 Dimenhydrinate injection Discontinuation or business decision 1998 Diphenhydramine hydrochloride injection Unknown 2001 Dobutamine hydrochloride injection Supply and demand 2001 Doxorubicin hydrochloride injection Manufacturing problems 2001 Epinephrine injection (Ana-Kit) Manufacturing problems 2001 Epinephrine injection (EpiEZPen) Discontinuation or business decision 1997 Ergonovine maleate injection Discontinuation or business decision 1999 Etanercept injection Supply and demand 2001 Ethacrynic acid tablets Business decision 2002 Ethinyl estradiol–norgestrel tablets (Lo/Ovral) Unknown 2002 Etomidate injection Unknown 2001 Factor IX injection Manufacturing problems 2001 Factor VIII injection Manufacturing problems 2001 Fenfluramine hydrochloride tablets Discontinuation or business decision 1997 Fentanyl citrate injection Business decision 2000

248 Am J Health-Syst Pharm—Vol 60 Feb 1, 2003 REPORTS Managing drug shortages

Table 1 (continued) Reason for Year Shortage Product Shortage Began Floxuridine injection Regulatory problems 2000 Flumazenil injection Regulatory problems 2000 Fluorescein sodium injection Unknown 1999 Flutamide tablets Unknown 2001 Furosemide injection Business decision 2002 Ganciclovir sodium injection Supply and demand 1999 Ganciclovir sodium injection Supply and demand 2001 Gelfoam powder and sponges Unknown 2000 Gelfoam powder and sponges Manufacturing problems 2001 Gentamicin sulfate injection Raw-material shortage 2001 Gentamicin sulfate preservative-free injection Raw-material shortage 2001 Glycopyrrolate injection Unknown 2001 Gold compounds (tablets and injection) Supply and demand 2001 Haemophilus b conjugate vaccine Manufacturing problems 2001 Heparin 5000-units/mL injection Manufacturing problems 2001 Hepatitis A vaccine Manufacturing problems 2001 Hepatitis B immune globulin injection Regulatory problems 1998 Hepatitis B immune globulin injection Unknown 2002 Hepatitis B vaccine Manufacturing problems 2001 Hyaluronidase injection Discontinuation or business decision 2000 Hydralazine hydrochloride injection Manufacturing problems 2001 Hydrochlorothiazide tablets Business decision 2002 Hydrocortisone cypionate oral suspension Discontinuation or business decision 2000 Hydromorphone hydrochloride injection Unknown 2001 Immune globulin injection Discontinuation or business decision 1997 Immune globulin injection (Gammimune) Supply and demand 2002 Indomethacin suppositories Discontinuation or business decision 2001 Infliximab injection Supply and demand 2001 Isoniazid injection Discontinuation or business decision 2001 Isoproterenol hydrochloride injection Raw-material shortage 2000 Leucovorin calcium tablets Unknown 2002 Levonorgestrel implant kit Manufacturing problems 2000 Levorphanol tartrate tablets and injection Unknown 2001 Levothyroxine sodium injection Manufacturing problems 2001 Levothyroxine sodium tablets Regulatory problems 2001 Lidocaine hydrochloride–epinephrine injection Unknown 2002 Lidocaine hydrochloride 2% viscous oral solution Manufacturing problems 2001 Lorazepam oral solution Unknown 2001 Lymphazurin radiopaque injection Manufacturing problems 2001 Lymphocyte immune globulin injection Manufacturing problems 2001 Measles virus vaccine live Manufacturing problems 2001 Measles, mumps, and rubella virus vaccine live Manufacturing problems 2001 Mechlorethamine hydrochloride injection Discontinuation or business decision 1999 Medroxyprogesterone acetate–estradiol cypionate injectable suspension Manufacturing problems 2002 Medroxyprogesterone acetate injection Unknown 2001 Mefloquine hydrochloride tablets Manufacturing problems 2002 Meningococcal polysaccharide vaccine (Menomune-A/C/Y/W-135) Unknown 2001 Meperidine hydrochloride injection Manufacturing problems 2001 Meropenem injection Supply and demand 2002 Mesalamine suppositories Manufacturing problems 2002 Methohexital sodium injection Regulatory problems 2002 Methylergonovine maleate injection Manufacturing problems 2002 Methylprednisolone acetate injectable suspension Manufacturing problems 2002 Methylprednisolone sodium succinate injection Raw-material shortage 2001 Methylprednisolone sodium succinate injection Supply and demand 2000 Metoclopramide hydrochloride injection Raw-material shortage 2001 Metoprolol tartrate injection Unknown 1999 Metyrapone capsules Manufacturing problems 2000 Mibefradil dihydrochloride tablets Discontinuation or business decision 1998 Midazolam hydrochloride injection Regulatory problems 2000 Minocycline hydrochloride capsules Unknown 2001 Mivacurium chloride injection Manufacturing problems 2001 Morphine sulfate injection Unknown 2002 Multivitamin injection (adult) Discontinuation or business decision 1997 Multivitamin injection (pediatric) Unknown 1997 Multivitamin injection (pediatric) Manufacturing problems 2001

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Table 1 (continued) Reason for Year Shortage Product Shortage Began Mumps skin test antigen Unknown 2002 Mumps virus vaccine live Manufacturing problems 2001 Mupirocin ointment Supply and demand 2001 Nalbuphine hydrochloride injection Unknown 2001 Naloxone hydrochloride injection Discontinuation or business decision 2001 Needles (BD Filter needles) Discontinuation or business decision 2001 Needles (Cyto-Safe) Discontinuation or business decision 2001 Neomycin sulfate oral suspension Manufacturing problems 1998 Nimodipine capsules Manufacturing problems 2001 Nisoldipine tablets Raw-material shortage 2001 Norepinephrine bitartrate injection Manufacturing problems 2001 Norethindrone tablets Unknown 2002 Nystatin pastilles Unknown 1999 Ondansetron hydrochloride injection Unknown 1999 Oseltamivir phosphate oral suspension and tablets Manufacturing problems 2001 Oxycel gauze Discontinuation or business decision 2001 Oxytocin injection Discontinuation or business decision 2001 Pancuronium bromide injection Raw-material shortage 2001 Pantoprazole sodium injection Manufacturing problems 2001 Paromomycin sulfate capsules Regulatory problems 2001 Paroxetine suspension Unknown 2002 Penicillin G sodium and penicillin G potassium injection Regulatory problems 1999 Pentobarbital sodium capsules Discontinuation or business decision 2001 Perphenazine oral concentrate Discontinuation or business decision 2000 Perphenazine tablets Unknown 2001 Phenobarbital sodium injection Raw-material shortage 1998 Phenobarbital sodium injection Raw-material shortage 2001 Phentolamine mesylate injection Manufacturing problems 2001 Piperacillin sodium injection Manufacturing problems 2001 Piperacillin sodium–tazobactam injection Natural disaster 1998 Piperacillin sodium–tazobactam injection Manufacturing problems 2001 Pneumoccocal vaccine polyvalent Raw-material shortage 2001 Pneumococcal 7-valent conjugate vaccine Supply and demand 2001 Potassium chloride tablets Manufacturing problems 2001 Pralidoxime chloride injection Unknown 2001 Procarbazine hydrochloride capsules Raw-material shortage 1998 Prochlorperazine edisylate injection Raw-material shortage 2001 Prochlorperazine maleate spansules Regulatory problems 1999 Prochlorperazine maleate spansules and prochlorperazine edisylate syrup Unknown 2001 Progesterone in oil injection Regulatory problems 1998 Promethazine hydrochloride injection Unknown 2001 Promethazine hydrochloride syrup Unknown 2001 Propofol injection Supply and demand 1998 Protamine sulfate injection Discontinuation or business decision 2001 Pyridoxine hydrochloride injection Unknown 2001 Quetiapine fumarate tablets Supply and demand 2001 Rabies immune globulin Manufacturing problems 2002 Ranitidine hydrochloride syrup Unknown 2001 Rapacuronium bromide injection Discontinuation or business decision 2001 Remifentanil hydrochloride injection Unknown 2001 Rifabutin capsules Unknown 2000 Rocuronium bromide injection Unknown 2002 Rotavirus vaccine live Discontinuation or business decision 1999 Rubella virus vaccine live Manufacturing problems 2001 Secobarbital sodium capsules Raw-material shortage 2001 Secretin injection Regulatory problems 1999 Sincalide injection Manufacturing problems 2001 Sodium chloride preservative-free injection (10-mL vials) Unknown 2002 Sodium pentothal injection Unknown 2001 Sodium tetradecyl sulfate injection Unknown 1997 Spectinomycin hydrochloride injection Discontinuation or business decision 2001 Stanozolol tablets Unknown 2001 Streptokinase injection Regulatory problems 2002 Streptomycin sulfate injection Supply and demand 1996 Stromectol tablets Unknown 1999 Succinylcholine chloride injection Raw-material shortage 2001

250 Am J Health-Syst Pharm—Vol 60 Feb 1, 2003 REPORTS Managing drug shortages

Table 1 (continued) Reason for Year Shortage Product Shortage Began Terbutaline sulfate injection Manufacturing problems 1996 Testosterone cypionate injection Manufacturing problems 2002 Testosterone in oil injection Regulatory problems 1998 Tetanus and diphtheria toxoids adsorbed Discontinuation or business decision 2000 Tetanus, diphtheria, and pertussis vaccine Discontinuation or business decision 2001 Thiamine hydrochloride injection Unknown 2001 Thioguanine tablets Manufacturing problems 2002 Thrombin powder Supply and demand 2001 Ticarcillin disodium–clavulanate potassium injection Regulatory problems 1999 Tirofiban hydrochloride injection Supply and demand 2001 Tobramycin sulfate powder for injection Manufacturing problems 2002 Tolazoline hydrochloride injection Discontinuation or business decision 2000 Tranexamic acid injection Manufacturing problems 1999 Tretinoin capsules Unknown 2001 Triamcinolone acetonide injection Supply and demand 2002 Triamcinolone diacetate injection Raw-material shortage 2001 Trihexyphenidyl hydrochloride tablets Unknown 2001 Triple sulfa vaginal cream Discontinuation or business decision 2001 Troglitazone tablets Discontinuation or business decision 2000 Tubocurarine chloride injection Discontinuation or business decision 2001 Urokinase injection Regulatory problems 1998 Valsartan tablets Manufacturing problems 2002 Vancomycin hydrochloride oral solution and capsules Raw-material shortage 2002 Varicella virus vaccine Manufacturing problems 2001 Vecuronium bromide injection Supply and demand 1999 Vinblastine sulfate injection Unknown 2002

Table 2. aging drug shortages. One limitation Impact of Drug Shortages on University of Utah Hospitals and Clinics, of our data is the number of shortag- January 1996 to June 2002 es noted between January 1996 and Impact Categorya No. (%) Shortages (n = 224) January 2001. From the more recent data, we know that UUHSC does not 1. No product available and no alternatives recommended 28 (13) experience every shortage that occurs 2. No product available, but nationwide. Another limitation is the alternatives recommended 68 (30) types of shortages tracked. Our focus 3. Available product rationed according to criteria 7 (3) was on agents used in the hospital 4. Could not obtain usual vial sizes or setting; however, UUHSC also com- product strengths 10 (4) prises many clinics and community 5. Able to manage through therapeutic interchange 2 (1) pharmacies. The clinics reported few 6. Product discontinued 29 (13) shortages to the DIS. Additionally, a 7. No impact 33 (19) majority of the shortages involved aCategories are listed in order of the severity of the impact, with category 1 being the most severe. parenteral agents rarely used in the community. Reasons for shortages were given by the manufacturers’ shortages (13%) increased costs, 73 creased drug costs; however, the or- customer service departments. Often, (33%) decreased costs, and 122 ganization had actually incurred a reason was not provided, so our data (54%) had an unknown or neutral costs due to prolonged cataract sur- may contain some inaccuracies. impact. This assessment did not in- geries and increased costs for treating Our data on the potential cost of clude the cost of investigating the patients with a drug extravasation. shortages may also have limitations. shortage and developing strategies This also would not have accounted It is difficult to quantify the increased for managing it, nor other indirect for the revenue lost to the organiza- cost of purchasing products off con- health care costs because the drug tion because of delays in procedures. tract or using more expensive alter- was not available. For instance, the native agents. Moreover, no patient unavailability of hyaluronidase, for Discussion outcomes were assessed, making it which there were no suitable alterna- This article describes our seven- difficult to judge how the overall cost tives, was classified as having de- year experience in tracking and man- of patient care may have changed.

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Table 3. sources that health care organizations Pharmacologic–Therapeutic Classification of Products are devoting to this problem. Costs Classification No. (%) Shortages (n = 224) could also be increased by medication errors when practitioners are forced Antihistamine drugs 1 (0) Antiinfective drugs 32 (14) to use unfamiliar agents. Antineoplastic agents 8 (4) Despite these limitations, our Autonomic drugs 21 (9) findings describe a situation of which Blood derivatives 1 (0) Blood formation and coagulation agents 11 (5) every health care organization is Cardiovascular drugs 13 (6) keenly aware. Hospital pharmacies Central nervous system agents 34 (15) have little means of forecasting po- Diagnostic agents 9 (4) Electrolytic, caloric, and water balance tential drug supply problems. When agents 7 (3) a problem does occur, the informa- Enzymes 1 (0) tion that is available is often extreme- Eye, ear, nose, and throat preparations 4 (2) Gastrointestinal drugs 8 (4) ly limited. Most manufacturers are Gold compounds 1 (0) not forthcoming about possible back Hormones 22 (10) orders or shortages because this Local anesthetics 2 (1) Oxytocics 4 (2) could hurt business. Manufacturers Serums, toxoids, and vaccines 23 (10) do have a variety of legal, public rela- Skin and mucous membrane agents 3 (1) tions, financial, and regulatory issues Vitamins 6 (3) Unclassified therapeutic agents 11 (5) to consider, but they may not appre- Devices 4 (2) ciate the impact on patients. While the Pharmaceutical Research and Manufacturers of America may describe the recent spate of shortages as Table 4. “overstated” and an “inconvenience,”6 Impact of Drug Shortages on Patient Safety, January 2001 to June any health-system pharmacist can 2002 point to a much more serious set of Safety Impact No. (%) Shortages (n = 109)a consequences for patients and health Alternative agent may cause more adverse care organizations. effects than item in short supply 15 (14) The problem of drug shortages is Item may be available only in a different strength or concentration than usual 20 (18) likely to persist or even worsen, given Shortage may cause a delay in therapy 8 (7) the unpredictability of manufactur- Alternative agent has different dosage ing problems and raw-material requirement than item in short supply 54 (50) Clinician may not be familiar with shortages, continuing consolidation alternative agent or formulation 3 (3) in the pharmaceutical industry, and Effect is immediate inventory practices. Optimal man- Minor severity5 2 (2) Major severity5 6 (6) agement and minimization of the Moderate severity5 15 (30) problem will involve analyzing the Effect is long-term and of moderate complex relationships among manu- severity5 4 (4) Item may be available only in different facturers, FDA, the producers of packaging than usual 24 (22) raw materials, wholesalers, payers, Clinicians may be unfamiliar with the health care practitioners, and pa- alternative product in terms of its mechanism of action, adverse effects, or tients. That this problem has attract- interactions 59 (54) ed the interest of the government, aPercentages do not total 100 because some shortages were associated with more than one potential safety health care institutions, and profes- impact. sional organizations is a promising development.7-9 Communication For example, a shortage of be- increased costs, health care organiza- with patients and within organiza- tamethasone may have prevented a tions may have lost revenue when tions is critical to limiting the impact woman giving premature birth from elective procedures were postponed of drug shortages. receiving antenatal corticosteroids. It or, as in the case of the corticosteroid would be difficult to quantify the suspension shortage, when proce- Conclusion total cost if the infant suffered lung dures could not be performed. These Detailed information on drug disease of prematurity. Aside from data do not capture the time and re- shortages monitored by UUHSC DIS

252 Am J Health-Syst Pharm—Vol 60 Feb 1, 2003 REPORTS Managing drug shortages from 1996 to 2002 indicated a trend tional shortage. Paper presented at ASHP 7. FDA fast track, priority review policies for Midyear Clinical Meeting. Orlando, FL; vaccines need expansion—GAO. FDC toward more frequent shortages. 1999 Dec 9. Rep. 2002; 64(Sep 23):19-20. 4. Behmer-Miller KA, Burke TG, Mutnick 8. Rx shortages could prompt congressional References AH. Dealing with the urokinase shortage: response, pharmacy exec warns. FDC Rep. 1. Rihn TL, Raval PJ, Vanscoy GJ. Managing management case study. Paper presented 2002; 64(Mar 4):20-1. the urokinase shortage: clinical and eco- at ASHP Midyear Clinical Meeting. Orlan- 9. U.S. General Accounting Office. State- nomic alternatives in peripheral arterial oc- do, FL; 1999 Dec 8. ment of Janet Heinrich, Director, Health clusion. Paper presented at ASHP Midyear 5. Department of Veterans Affairs National Care—Public Health Issues. Testimony Clinical Meeting. Orlando, FL; 1999 Dec 6. Center for Patient Safety. Healthcare Fail- before the Subcommittee on Public 2. Goldberger MJ, Hubbard LM. FDA’s role ure Modes and Effects Analysis. www. Health, Committee on Health, Education, in drug shortages. Paper presented at patientsafety.gov/HFMEAIntro.pdf (ac- Labor, and Pensions, U.S. Senate. Child- ASHP Annual Meeting. Los Angeles, CA; cessed 2002 Sep 30). hood vaccines: challenges in preventing 2000 Jun 4. 6. Haugh R, Thrall TT, Scalise D. A precrip- future shortages. GAO-02-1105T. www. 3. Chan MK. Management of intravenous tion for concern. Hosp Health Netw. 2002; gao.gov/new.items/d021105t.pdf (access- immune globulin utilization during a na- 76:44-7. ed 2002 Sep 30).

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