Drug shortages have become more severe in recent years; however, data describing how such shortages impact gastroenterology (GI) drugs are limited. We characterize longitudinal trends of drug shortages in the USA within the scope of GI practice.
Drug shortage data from the University of Utah Drug Information Service were analyzed from January 2001 to December 2014. A board certified gastroenterologist, an internal medicine physician, and a clinical pharmacist identified drug shortages within the scope of GI practice, whether they are used for high-acuity conditions, availability, formulation, or therapeutic category. Trends in the length of shortages for GI drugs were described using standard descriptive statistics and regression analysis.
A total of 1,774 drug shortages were reported over the 14-year period. Of those, 253 shortages (14.3%) were classified within the scope of GI practice. The number of newly-reported GI drug shortages increased from 15 in 2001 to 44 in 2014. The majority of GI drugs (55.7%) were parenteral and 102 shortages (40.3%) were single source drugs. By the end of the study period, 44 (17.4%) GI drugs remained on active shortage with a median duration of 24.3 months (interquartile range [IQR] 6.9-32.1). The median duration for resolved shortages of GI drugs was 7.7 months (IQR 2.9-17.6).
There was a significant increase in shortages of drugs used in GI practice from 2001 to 2014. Many of these drugs were used for high-acuity conditions and alternative agents were also impacted. Gastroenterologists must be cognizant of current shortages in order to mitigate impact on patient care.
Med Access @ point care 2017; 1(1): e58 - e64
Article Type: RESEARCH @ POINT OF CARE
AuthorsJigar M. Patel, Erin R. Fox, Mark Zocchi, Zone-En Lee, Maryann Mazer-Amirshahi
- • Accepted on 14/06/2017
- • Available online on 11/07/2017
- • Published online on 12/07/2017
This article is available as full text PDF.
Drug shortages are an important issue in public health and medical care delivery (1). The U.S. Food and Drug Administration (FDA) defines a drug shortage as “a situation in which the total supply of all clinically interchangeable versions of an FDA-regulated drug product is inadequate to meet the projected demand at the user level” (2). For this study, we used the American Society of Health-System Pharmacists (ASHP) definition which describes a drug shortage as “a supply issue that affects how the pharmacy prepares or dispenses a drug product or influences patient care when prescribers must use an alternative agent” (3). In recent years, there have been dramatic increases in drug shortages. In 2005, the FDA’s Drug Shortage Program (DSP) reported shortages of 61 medications and this number increased more than fourfold, to 251 medications by 2011 (4). Although that number significantly decreased to 117 shortages in 2012, 44 new shortages in 2013, and 44 new shortages in 2014, shortages continue to pose a real challenge to public health (4).
There are several reasons for drug shortages, including manufacturer mergers, facility consolidation, manufacturing quality issues, and narrow profit margins for generic drugs (5). Shortages have the potential to impact patient care in a variety of ways and have been associated with treatment delays, lack of treatment when indicated, medication errors, and even patient deaths. In a 2010 hospital survey, 89% of the responding hospitals reported drug shortages that may have caused a medication safety issue or an error in patient care (6). In addition, shortages increase the cost of patient care.
Shortages have been described in the literature for other specialties, such as infectious disease (7) and acute care medications (8); however, there are limited data describing how shortages impact gastroenterology (GI) drugs. In this study, we characterize longitudinal trends in USA drug shortages within the scope of GI practice from 2001 to 2014.
The University of Utah Drug Information Service (UUDIS) has been collecting drug shortage data since January 2001 and publishes critical drug shortage information on a public website (
UUDIS collects the following drug shortage data using Microsoft® Excel 2007; the generic product name, the therapeutic category, the date the shortage began (date UUDIS was notified), the resolved date, the duration, the reason for the shortage, the controlled substance schedule (if applicable), and whether or not the drug is an injectable product. Drug shortages that occur due to a product discontinuation or withdrawal from the market have the same start and stop date for a duration of zero days (9).
The data set was restricted to shortages that occurred between January 1, 2001 and December 31, 2014. A board certified gastroenterologist, an internal medicine physician, and a clinical pharmacist identified drug shortages within the scope of GI practice. All discrepancies were discussed until a consensus was reached. High-acuity conditions were either life threatening or severe enough requiring immediate intervention, such as GI bleeding and infections. We then categorized the included medications according to whether they are used for high-acuity conditions, marketing status (brand vs. generic), formulation (parenteral vs. other routes of administration), and if the drug is a single-source product (produced by a single manufacturer). We also determined the number of times a medication had been in short supply as well as the availability of a substitute therapy and whether the alternative was also affected by a shortage at any time during the study period. For some portions of the analysis, products were grouped together based on therapeutic category. Trends in the length of shortages for GI drugs were described using standard descriptive statistics and regression analysis. Discontinued products were not included in the analyses of shortage time. A p value of <0.05 was considered significant. Data were analyzed using Stata 13.1 (College Station). The data do not meet the definition of human subjects’ research, and therefore were exempt from Institutional Review Board review. A comprehensive list of products affected by shortages is provided in a supplemental appendix (available online as supplementary material at medicine-access.pointofcarejournals.com).
Number and duration of shortages
There were 1,774 drug shortages reported over the 14-year study period. Of those, 253 shortages (14.3%) were classified as being within the scope of GI practice. The number of reported GI drug shortages increased from 15 in 2001 to 44 for the year 2014, peaking in 2012 at 46 (
Number of reported gastrointestinal drug shortages by year.
Types of medications impacted
Of all GI drug shortages, 56 (22.1%) were for drugs used for high-acuity conditions. The majority of GI drugs (55.7%) were parenteral products. Generic drugs were impacted more by shortages (65.2%), and 102 shortages (40.3%) were single-source drugs. Median shortage duration for nonparenteral products was 7.2 months (IQR 2.4-15.6) compared to 9.6 months (IQR 4.1-26.8) for parental products with a Hodges-Lehmann median difference (12) of 2.8 months (95% CI, 0.6%-5.4%). Generic drugs had a median shortage duration of 10.5 months (IQR 4.8-25.0) compared to 5.5 months (IQR 1.4-14.0) for brand-name drugs with a Hodges-Lehmann median difference of 3.9 months (95% CI, 1.8%-6.5%). Single-source drugs had a median shortage duration of 5.3 months (IQR 1.3-11.9) compared to 11.6 months for drugs that were not from a single source (IQR 5.1-27.3), with a Hodges-Lehmann median difference of 5.6 months (95% CI, 3.3%-8.0%). Shortage duration for high-acuity drugs did not significantly differ from nonhigh-acuity drugs.
Almost all (92.1%) of the GI drugs impacted by shortages had a therapeutic alternative, but more than one-third of these alternatives (34.0%) were also impacted by shortage at some point during the study period (
High acuity drugs without alternative or alternatives also impacted
|Type of medication||Number of shortages||Total months on shortage||Percentage of study period on shortage|
|Alternative also impacted|
|Lactated Ringe’s solution||2||11.2||6.6%|
Infectious disease drugs were the most common GI drugs on shortage, with 53 (20.9%) drug shortages totaling 790.3 months (65.9 years) during the study period, and a median duration of 10.3 months (IQR 3.8-25.1). Other commonly impacted classes of medications included those used to treat motility disorders, inflammatory bowel disease, and acid suppression, and drugs used for diagnostic and endoscopic procedures (
Types of gastroenterology drugs affected by shortages
|Therapeutic category||Number of shortages||Percentage of shortages||Total shortage months||Median shortage months (IQR)|
|IQR = interquartile range.|
|Acid suppressants||28||11.1%||296.0||5.5 (2.4-18.1)|
|Contrast agent||4||1.6%||44.3||6.6 (3.4-18.7)|
|Fluids, electrolytes, nutrition||15||5.9%||88.6||3.6 (1.3-8.2)|
|Infectious disease||53||20.9%||838.1||10.3 (3.8-25.1)|
|Inflammatory bowel disease||33||13%||549.9||9.4 (3.6-30.6)|
|Irritable bowel syndrome||10||4.0%||93.9||8.0 (3.8-15.6)|
Reasons for shortage
In many cases, the manufacturer did not provide the reason for shortage (n = 121). When a reason was provided, the most common reason for shortage was manufacturing problems (27%) followed by supply/demand (11%), and raw materials (6%). Median shortage duration for manufacturing problems was 11.6 months (IQR 4.9-28.3), supply and demand was 8.6 months (IQR 3.5-18.5), and raw materials was 18.6 months (IQR 2.9-34.2) (
Reasons for gastroenterology drug shortages
|Reason for shortage||Number of shortages||Percentage of shortages||Median shortage months|
|NA = not applicable.|
|Discontinued drugs not included in shortage month calculations.|
|Business decision||5||2%||0.5 (0.0-3.9)|
|Manufacturing problems||67||26%||11.6 (4.9-28.3)|
|Natural disaster||3||1%||6.1 (6.1-6.2)|
|Raw materials||15||6%||18.6 (2.9-34.2)|
We found a significant increase in shortages of drugs used in GI practice over the 14-year study period (2001-2014). In addition, several drugs had multiple shortages with long total cumulative durations. Drug shortages have previously been reported to have a significant impact on patient care since they limit the treatment options available to prescribers and patients (13). They also add substantial cost to the healthcare system (13). Our paper stands out in that it highlights drug shortages in GI practice over a long period of time, highlighting a trend of increased drug shortages year after year.
An online survey conducted by the American Society for Gastrointestinal Endoscopy (ASGE) Health and Public Policy Committee showed that a large percentage of GI practices have experienced significant shortages in drugs used for sedation during endoscopic procedures and the management of GI bleeding (14). A survey of American College of Gastroenterology (ACG) members showed that intravenous sedation was administered in 98.2% of esophagogastroduodenoscopies (EGDs) and 98.8% of colonoscopies (15). Approximately three-fourths of those surveyed reported using conventional sedation (a benzodiazepine, e.g., midazolam with an opioid analgesic, e.g., fentanyl) while 25.7% utilized propofol-based sedation (15). We found that drug shortages for midazolam, fentanyl, and propofol, which are the first-line sedatives, existed at some point in time during our study period (
Medications in short supply used for sedation in gastrointestinal procedures
|Product||Number of times in short supply||Total months short|
In a letter to the FDA, the ACG has also addressed concerns regarding a shortage of sedative drugs used in endoscopy centers and hospitals (17). Such drug shortages have forced practices to cancel procedures, and have increased costs to the healthcare system as gastroenterologists are forced to substitute moderate sedatives with other sedatives, such as propofol, which may require additional training or the presence of an anesthesia professional (17).
In addition, the ASGE guideline for sedation and anesthesia in GI endoscopy mandates that specific antagonists of opioids (naloxone) and benzodiazepines (flumazenil) should be present and readily available in every endoscopy unit. Our study found drug shortages for both naloxone and flumazenil over the years (16). These findings are consistent with ASGE’s Health and Public Policy Committee’s national online survey (14).
Antiinfective agents and drugs used in management of inflammatory bowel disease were the two most impacted groups in this study. Although substitutes are available for most of these agents, it must be highlighted that there was a rising trend in the increase of drug shortages in these categories over the study period, as well as an increased burden of cost to the healthcare system. For example, drug shortages were seen for both metronidazole and oral vancomycin, which are used for the treatment of the
We also found significant shortages for parenteral nutrition ingredients and micronutrients. A recent New York Times article highlighted the story of a Cleveland patient with Crohn’s disease who was unaware that zinc had been removed from her daily intravenous (IV) nutrition until she developed side effects from the deficiency (21). In response to this news, Dr. Heller from the Crohn’s & Colitis Foundation of America (CCFA) recommended that doctors keep patients informed of therapy changes and ensure that they are educated and empowered to make the best decisions about their care (22). Most patients want to be informed regarding drug shortages that might affect their care, even if the severity of potential side effects is small (23).
Another category of drug shortage of high importance is that of vaccines. Prevention is better than cure, and this is especially true for vaccine-preventable diseases. There were multiple shortages of both vaccines against hepatitis A and B viruses during the study period. In this study, we found a reported shortage of 50 months for the hepatitis B virus (HBV) vaccine. Hepatitis B vaccination of individuals at a high risk of acquiring the virus, including healthcare workers, is highly recommended as per the Centers for Disease Control and Prevention (CDC) guidelines and has effectively been shown to reduce the incidence of newly infected cases in society (24). During 2000-2004, self-reported hepatitis B vaccination coverage among adults at risk for HBV infection increased from 30% to 45%; this increase in vaccination coverage likely contributed to the 35% decline in acute hepatitis B incidence that occurred during this period (25).
Our study found significant drug shortages for epinephrine and IV proton pump inhibitors (PPIs), which are used for the management of acute GI bleeding, and could be life-saving measures. The combined shortage of IV PPIs was 9 months over the 14-year period. One study found that only 50% of upper GI hemorrhage (UGIH) patients received IV PPI for an appropriate indication, and that only 33% of non-UGIH patients were truly nil by mouth (26). Strict adherence to evidence-based guidelines from professional societies for the use of these agents can reduce unnecessary use, and can help mitigate drug shortages as well as healthcare costs while maintaining the utmost standard of care. Two prospective studies found no acceptable indication for IV PPI in 56% of patients during their hospitalization (27). Newer formulations and drugs can also help reduce drug demand. One such example is the introduction of new oral PPI products that can be administered as a suspension expanded the therapeutic options for critically ill patients (28).
While relatively few in number, shortages of diagnostic agents for GI procedures can post serious problems. For example, shortages of sincalide impacted patient care due to the lack of pharmaceutical alternatives and the potential delay in evaluating gall bladder function. Some clinicians substituted a large amount of fat for sincalide, but this substitute is not appropriate for most patients. Shortages of both indigo carmine as well as methylene blue seriously impacted endoscopic procedures, specifically chromoendoscopy, which aids in the identification of Barrett’s esophagus and the characterization of colonic polyps/dysplasia. A shortage of both dyes at the same time left no alternatives for clinicians.
Physicians should be cognizant of medication errors and adverse drug events, which may occur as a result of shortages. Substituting medications can result in errors as the prescriber and nursing staff may be less familiar with available alternatives, specifically dealing with proper dosing, administration protocols, and contraindications (29). In addition, different strengths or concentrations may be stocked because of limited availability of the product that is usually stocked. In one case, a patient was overdosed with ketamine due to a diluting error, which resulted in confusion and delirium during a GI endoscopic procedure (30). In this situation, a shortage of ketamine in 10 mg/mL strength had resulted in the hospital having to stock the 50 mg/mL concentration in an operating room automated dispensing cabinet. In order to protect the safety of patients, ASGE endorses the CDC’s safe practice guideline, which states that shortages of some essential medications may warrant the implementation of meticulously applied practice and quality standards to subdivide contents of single-dose/single-use vials (31). Another way to prevent such errors is to have regular staff meetings, optimize communication to staff about current shortages, have protocols in place for the use of alternative therapies, and to have staff assigned to monitor medication changes (17).
The major limitation of this study was that we could not assess the actual impact that shortages had on individual institutions or on patient care – either in the form of delayed or suboptimal therapy or in terms of resultant medication errors and adverse outcomes. Also, we could not describe the severity of shortages affecting a particular product (e.g., whether the product was in limited supply or completely unavailable). There were limited data pertaining to the comparative efficacy of some therapeutic alternatives that were identified, and we did not take into account additional costs or toxicity when considering the use of substitutes. The duration of unresolved shortages would have been underestimated using our methodology. Finally, we could not account for the time and resources used by institutions to mitigate drug shortages. These are all potential areas for additional prospective study.
There was a significant number of drug shortages affecting drugs used in gastroenterology during the study period. The shortages were the result of several different factors that affected the manufacturing process and access to these medications. The impact of these shortages has been felt by the medical system as a whole, but further research is needed at the patient-outcome level. Future research should evaluate patient harm and the increase in healthcare costs derived from these shortages. It is the responsibility of everyone involved in the healthcare system – the pharmaceutical industry, the FDA, health care institutions, and clinicians – to identify shortages as quickly as possible and to implement mitigation strategies before they become critical (32).
Cohen SH Gerding DN Johnson S et al. Society for Healthcare Epidemiology of America; Infectious Diseases Society of America. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the society for healthcare epidemiology of America (SHEA) and the infectious diseases society of America (IDSA). 2010 31 5 431 455
Mast EE Weinbaum CM Fiore AE et al. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) Part II: immunization of adults. 2006 55 Rr-16 1 33 quiz CE1-4.
- Patel, Jigar M. [PubMed] [Google Scholar] 1, * Corresponding Author (Jigar_patel@prodigy.net)
- Fox, Erin R. [PubMed] [Google Scholar] 2
- Zocchi, Mark [PubMed] [Google Scholar] 3
- Lee, Zone-En [PubMed] [Google Scholar] 4
- Mazer-Amirshahi, Maryann [PubMed] [Google Scholar] 5
Department of Internal Medicine, MedStar Washington Hospital Center, Washington, DC - USA
Drug Information Service, University of Utah Health Care, Salt Lake City, Utah - USA
Center for Healthcare Innovation and Policy Research, George Washington University School of Medicine and Health Sciences, Washington, DC - USA
Department of Gastroenterology, MedStar Georgetown University Hospital, Washington Hospital Center, Washington, DC - USA
Department of Emergency Medicine, Georgetown University School of Medicine, MedStar Washington Hospital Center, Washington, DC - USA
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