1. Critical Drug Shortages: A Major Public Health Problem That Affects Us All and How To Deal With It Philip M. Rosoff, M.D., M.A. Professor of Pediatrics & Medicine Chair, Duke Hospital Ethics Committee Duke University Medical Center Durham, NC 1

2. Critical Drug Shortages In the US (and Western Europe) we have been increasingly afflicted with unexpected and prolonged shortages of important drugs. This can be due to a variety of reasons: –A business decision –A manufacturing problem –A base materials supply problem 2

3. FDA Current Shortages (as of 7/19/2011) Acetylcysteine Inhalation Solution Amikacin Injection Amino Acid Injection Ammonium Chloride Injection Ammonium molybdate injection Sodium phenylacetate and sodium benzoate Injection 10%/10% Amphetamine Mixed Salts, ER Capsules Aquasol A, 50,000 units/mL, 2 mL ampule Arginine 10% injection (R-Gene 10) Avalide (irbesartan and hydrochlorothiazide)Tablets Bleomycin Injection Calcitriol 1 mcg/mL Injection Calcium Chloride Injection Calcium Gluconate Cisplatin injection 1 mg/mL solution Cleviprex Cyanocobalamin injection Cytarabine Injection Daunorubicin hydrochloride solution Desmopressin Injection Dexamethasone Injection Digoxin Injection Diltiazem Injection Doxorubicin (adriamycin) lyophilized powder Doxorubicin Liposomal (Doxil) Injection Doxorubicin Solution for Injection Ethiodol (ETHIODIZED OIL) ampules Etoposide solution for injection Fabrazyme (agalsidase beta) Foscarnet Sodium Injection Fosphenytoin Sodium Injection Furosemide Injection Haloperidol Decanoate Injection Intravenous Fat Emulsion Leucovorin Calcium Lyophilized Powder for Injection Leuprolide Injection Levoleucovorin (Fusilev) 50 mg single use vials Levorphanol 2mg Tablets Lorazepam Injection Magnesium Sulfate Injection Methylphenidate HCl Metoclopramide injection Mexiletine Capsules (150mg, 200mg, and 250mg) Mitomycin Powder for Injection Mustargen (mechlorethamine HCl) injection Multi-Vitamin Infusion (Adult and pediatric) Nalbuphine Injection NeoProfen (ibuprofen lysine) Injection Neostigmine methylsulfate injection rotigotine transdermal system Norepinephrine Bitartrate Injection Oxsoralen (methoxsalen) 1% topical lotion Oxsoralen-Ultra (methoxsalen) 10 mg capsules Phenylephrine HCl Injection Potassium Phosphate Procainamide HCL Injection Propofol Injection Sodium Chloride 23.4% Sodium Chloride 14.6% Injection Sodium Phosphate Injection Sulfamethoxazole 80mg/trimethoprim 16mg/ml injection Tamiflu for Oral Suspension Thiotepa for Injection thyrotropin alfa Thyrolar Tablets Vasopressin Injection Vecuronium Injection 3

4. (Partial) Drug Shortage List from ASHSP* (more comprehensive and up-to-date than FDA) 4 *American Society of Health-System Pharmacists

5. Tragic Choices In late December, 2010, we experienced a critical shortage of cytarabine, a chemotherapy drug that is integrally important in curative therapy for adult and childhood acute myelogenous leukemia (AML) and childhood acute lymphoblastic leukemia (ALL). We came within 2 days of completely running out. What to do if we have enough for one person and two people need it? How do you choose? 5 Also see PM Rosoff (2011): AJOB (in press)

6. How Should We Decide? What rules would you use? Would you permit some forms of discrimination? 6

7. Faced With A Critical Shortage, How Should We Decide Who Gets The Drug When Not All Can? First come, first served? A coin toss or lottery? What should be the role of medical/scientific evidence? Should there be “special” patients (i.e., VIPs)? Should some people be a priori excluded? –For example, undocumented immigrants, prisoners, patients with a prior history of poor compliance? 7

8. Unresolved Questions Do we owe a greater “loyalty” to patients who live in NC than those referred from elsewhere? What do we do with patients who hear that we may have the drug they need, but are not Duke patients (for example, they are UNC patients)? Should we privilege the young over the old? –For instance children with AML have a 60% chance of cure, while adults have a 30% (of course, this is a population-derived statistic). Does that mean we should give the limited supply of cytarabine to children and not adults? Do patients on therapy have a greater claim to drug than new patients who might have a better chance of cure? Should we stop treatment of patients receiving a drug for unsupported (by evidence) reasons in order to conserve supplies? Should “dying” patients have claim to any drugs other than “comfort” drugs during a shortage? 8