Drug shortages are a growing concern for most hospital pharmacists today. When a drug shortage occurs, a pharmacist must often stop everything to focus on the emergency at hand. Additionally, these shortages are increasingly becoming a patient safety issue as alternatives are substituted or different formulations or packages of products are used.
Drug shortages occur for a variety of reasons, including manufacturing or regulatory problems, supply and demand increases, raw material shortages, or business decisions to discontinue products.1-3 Often the true cause of a shortage is unknown, because the manufacturer will not provide the reason.1-3
A good example of how manufacturing or regulatory problems can lead to a drug shortage is the current problem with Paxil CRT and Avandamet® tablets. GlaxoSmithKline was having manufacturing problems at their Puerto Rico plant, and on March 4, 2005, the US Food and Drug Administration (FDA) requested that federal marshals seize all unsold US shipments of these agents.4 The issue with the Paxil CRT tablets was that the tablets could split apart, negating the controlled-release effect. The Avandamet® tablets were problematic because they contained inaccurate amounts of rosiglitazone, one of the components of Avandamet®. As a result of these problems, GlaxoSmithKline signed a consent decree with the FDA.5 A consent decree is more serious than a warning letter or citation, and a company enters into a consent decree with the FDA only after the government has decided to take legal action against a company. This usually occurs when a company has received many warnings, but has not corrected the problems. Once a company enters into a consent decree, the legal action is dropped and the company works closely with the FDA to remedy the violations.6
|Regardless of why a drug shortage occurs, pharmacists must devise management strategies to ensure
patients continue to
receive excellent care.
The FDA can intervene and allow products from other countries, such as Canada, to be used in the United States during severe shortages of medically necessary drugs.7 A recent example of this is the methotrexate injection shortage. In 2004, a plant that supplied approximately 85% of the United States' market closed due to quality control problems.8 To avert a severe shortage, the FDA allowed Mayne Pharma to sell methotrexate injection from Canada in the United States.
Regardless of why a drug shortage occurs, pharmacists must devise management strategies to ensure patients continue to receive excellent care. Information on managing drug shortages is available at www.ashp.org/shortage. This Website outlines current availability issues and describes methods for obtaining products, such as direct orders or drop shipments. For more severe shortages, this Website provides detailed shortage management suggestions, including alternative agents. Pharmacists may consult this Website if they are having trouble ordering a specific product. Pharmacists can also report a shortage if the agent in question is not listed.
When faced with a shortage, first determine the supply available. This will guide your overall management strategy. If no product is available, management strategies include using an alternative agent, delaying therapy, or foregoing treatment. The specific strategy used will depend on the agent in question. For example, if no rocuronium is available, other neuromuscular blocking agents may be used as alternatives. If pneumococcal 7-valent conjugate vaccine (Prevnar) is in short supply, immunizations may be delayed until product is available. Benzylpenicilloyl polylysine injection (Pre-Pen) is no longer available,9 and many clinicians are choosing to forego penicillin skin testing.
The duration of most drug shortages is difficult to estimate. Manufacturers can often give an approximate date for when product will be available, but these estimates are often pushed back as the company fills backorders from the shortage. The product type and reason for a shortage may provide a clue about the potential duration of a shortage. For example, biologic agents, including vaccines, take multiple steps to prepare and require significant regulatory action before a lot may be released for sale. These shortages take longer to resolve, simply because of the greater time required in the manufacturing process. Some products, such as cephalosporins or penicillins, require a separate factory for manufacturing.
The most difficult shortage situation to manage effectively is when a small amount of product is still available. Depending on the situation, it may make sense to use the product until it is gone and then manage the shortage as you would if no product were available. For example, nimodipine is chiefly used in a select group of patients with subarachnoid hemorrhage. It would be impossible to determine which patients might deserve the drug more than others, so when faced with a nimodipine shortage, the strategy to use remaining supplies until gone fits best. When faced with a shortage of a drug that is used in a small number of patients for a potentially life-saving indication, it may make sense to reserve product. For example, betamethasone acetate/ betamethasone sodium phosphate suspension for injection (Celestone Soluspan) is used in a variety of ways to relieve pain.10 However, the drug is also used for premature infant lung maturation in women at risk for preterm delivery.10 During a Celestone Soluspan shortage, clinicians may choose to reserve drug for this indication and use alternative agents for pain relief. Decisions to allocate product for specific patients are best made by the Pharmacy and Therapeutics Committee or medical staff.
|Communication of the
management plan as soon
as possible is key with any
Drug shortages are not only frustrating, but also a potential patient safety issue. Patients are at risk when prescribers must use unfamiliar alternative agents. The dosing, adverse effects, and drug interactions for these alternative agents may be quite different from the product they are used to using. Additionally, there may be few data published regarding the use of alternative agents.
Communication of the management plan as soon as possible is key with any drug shortage. Try to involve stakeholder clinicians as early as possible and notify all pharmacy staff, not just pharmacists. E-mail is an efficient tool, particularly when notifying selected groups of clinicians. Keep staff updated about when additional supplies will be available and when alternative agents must be used. Provide education about alternative agents, particularly if the dosing, adverse effects, or drug interactions differ from the product that is in short supply.
Drug shortages are unpredictable and a growing concern. Shortages are also a patient safety issue. Resources such as the American Society of Health-System Pharmacists (ASHP) Drug Shortages Resource Center can provide important details and management strategies.
- ASHP guidelines on managing drug product shortages. Am J Health Syst Pharm. Aug 1 2001;58(15):1445-1450.
- Fox ER, Tyler LS. One pharmacy's approach to managing drug shortages. Am J Health Syst Pharm. Jan 1 2003;60(1):27, 31.
- Fox ER, Tyler LS. Managing drug shortages: Seven years' experience at one health system. Am J Health Syst Pharm. Feb 1 2003;60(3):245-253.
- Anon. U.S. Marshals Seize Lots of GlaxoSmithKline's Paxil CR and Avandamet Tablets Because of Continuing Good Manufacturing Practice Violations. Available at http://www.fda.gov/bbs/topics/news/2005/NEW01162.html. Updated March 4, 2005. Accessed March 4, 2005: U.S. Food and Drug Administration, Rockville, MD; 2005.
- PressWIRE. US FDA: GlaxoSmithKline signs consent decree with FDA; Agrees to correct manufacturing deficiencies. NewsEdge. May 3 2005.
- Anon. FDA systems-based inspection approach to be expanded by early 2002. The Pink Sheet. November 19 2001:28.
- Jensen V, Kimzey LM, Goldberger MJ. FDA's role in responding to drug shortages. Am J Health Syst Pharm. Aug 1 2002;59(15):1423-1425.
- Marcus AD. Critical Cancer Drug Faces Shortage. Wall Street Journal. March 15 2005:D1.
- University of Utah Drug Information Service. Drug Products With Limited Availability - Drug Products No Longer Available. Updated April 14, 2005. Accessed June 11, 2005. Available at http://www.ashp.org/shortage/not-available-notices.cfm: American Society of Health-System Pharmacists.
- Fox ER, Mullin SM. Injectable Corticosteroid Suspensions. Updated May 3, 2005. Accessed June 11, 2005. Available at http://www.ashp.org/shortage/celestone.cfm: American Society of Health-System Pharmacists; 2005.