Antimicrobial drug shortages

January 2005

The shortage of influenza vaccine this season had a significant impact on many practitioners and patients. For weeks, the topic was the focus of intense media coverage. High-risk individuals lined up for hours to receive the limited vaccine supplies while others went without. The logistics of managing this shortage affected health care professionals from state health departments to individual clinic practices, where new policies had to be developed to handle vaccine allocation and ensure that the limited supplies reached those most in need.

Unfortunately, this is not an isolated case of medication shortage affecting the infectious disease practitioner. Many remember that influenza vaccine shortages also occurred in the 2002-2003 and 2003-2004 influenza seasons. The past three years have also seen their share of antimicrobial drug shortages. Some recent examples that have now resolved include piperacillin-tazobactam (Zosyn, Wyeth), caspofungin (Cancidas, Merck) and piperacillin. In fact, of the 13 drugs currently listed on the FDA Web site of drug shortages, five (38%) are anti-infective agents (see Table 1), and four vaccines in addition to influenza vaccine are included on the list of drug products with limited availability. This recent rise in antimicrobial drug shortages does not seem to be a transient problem. Although these lapses in supply cannot be anticipated, it has become clear that practitioners should have a plan in place to handle these situations when they arise (see Table 1).

It is important for practitioners to understand the terminology surrounding drugs with reduced availability. The FDA has specific criteria for listing a drug as a shortage; therefore, not all agents with reduced availability can be identified through the FDA listing.

The FDA defines a drug shortage as follows:

• The total supply of all versions of the approved product available at the market level will not meet the current demand AND
• A registered alternative manufacturer will not meet the current and/or projected demands for the potentially medically necessary use(s) at the user level.

There are many different types of drug shortages that can be encountered. Not all shortages imply that the drug is completely unavailable. These cases of absolute shortage are relatively rare. What is more common is a relative shortage, where some drug is available, but the restricted supply must be rationed in some way. This allocation can occur at the institutional or national level.

Understanding the causes

It is important to understand the type of shortage and the cause to best assess potential impact from these situations on an individual institution or provider, as not all drug shortages will impact a wide range of practitioners. For example, of more than 224 drug shortages reported over a seven-year period at a Utah health system, only 75% directly impacted the institution due to the degree or duration of the shortage and the formulary status of given agents at that time (Am J Health Syst Pharm. 2003;60:245-253).

Causes of shortages can include lack of raw materials, damage to an existing supply, manufacturing difficulties, recalls and unexpected increases in demand. Each of these has been linked to common drug shortages over the past 18 months. The length of the shortage is often determined by the ultimate cause of the problem and the ability of the manufacturer to control these circumstances. The first step in handling the announcement of a drug shortage is to determine whether or not the specific agent is one commonly used in your individual practice setting and then what the anticipated duration will be.

Facing the consequences

The consequences of these shortages can be felt at many levels. First and most important is the care of the individual patient. When an agent becomes unavailable, first-line therapeutic options may not be given to patients with serious diseases. This can be seen with the current, ongoing penicillin shortage. Penicillin G was first reported as a drug on shortage in the summer of 1999. In a survey conducted through the Emerging Infection Network approximately one year into the shortage, 82% of nearly 500 practitioners had changed a therapeutic regimen as a result of the shortage. The estimated number of patients affected by that time in the shortage was more than 2,000. Currently, supplies of penicillin G can be obtained but are often reserved for patients with congenital syphilis, neurosyphilis and other conditions where penicillin is clearly the drug of choice.

Another consequence affecting patients is the potential for increased cost of care. Often, when an agent is not available, the only alternatives are more expensive. The most prominent example of this was the shortage of amphotericin B deoxycholate, during which most patients were converted to the lipid formulations of amphotericin B, with a five- to 10-fold increase in cost of daily treatment. For antibacterial agents, the drug may not only be more expensive, but also have a broader spectrum of activity. The consequences of this change could theoretically lead to increased resistance profiles at the patient or institutional level. Finally, not all drugs carry the same safety profile, and the cost of changing therapy may be increased toxicities from the alternative agent selected.

When shortages occur, they can have significant impact on health systems as well. As seen with the recent influenza vaccine example, new policies need to be developed to handle the limited supply of the agent in short supply as well as determine appropriate alternative therapies. Since these often occur without prior warning, advance planning for individual situations is not feasible. A more logical approach is to compile a list of key individuals that should be involved in managing a shortage that can be supplemented with key thought leaders in the therapeutic area impacted by the individual scenario. The American Society of Health-System Pharmacists has prepared a guidance document that reviews the process of addressing individual drug shortages (Am J Health Syst Pharm. 2001;58:1445-1450).

In addition, many of the same consequences felt by patients can be magnified throughout the health system following a drug shortage, including cost, resistance and lack of first-line therapies for serious infections (see Table 2).

Drug shortages are a problem that will continue to affect the infectious disease community. Having a reasonable plan to address these problems as they arise is the most prudent strategy to help practitioners handle these ongoing interruptions in drug supply.

For more information:

• Fox ER and Tyler LS. Managing drug shortages: seven years’ experience at one health system. Am J Health Syst Pharm. 2003;60:245-253.
• ASHP Council on Administrative Affairs, American Society of Health-System Pharmacists. ASHP guidelines on managing drug product shortages. Am J Health Syst Pharm. 2001;58(15):1445-1450.

• Elizabeth Dodds Ashley, PharmD, BCPS, Division of Infectious Diseases, Duke University Medical Center, Durham, N.C.