Featured Articles

Special Issue: Drug shortages: National Survey Reveals High Level of Frustration, Low Level of Safety

An exhaustive account of frustrations, difficulties, and patient safety concerns came across loud and clear from more than 1,800 healthcare practitioners (68% pharmacists) who participated in our July-September 2010 survey on drug shortages.1 Many respondents stated that the conditions associated with drug shortages during the past year have been the worst ever, without a glimmer of hope for any improvement in the near future. They feel unsupported by the Food and Drug Administration (FDA) and perplexed regarding why the US is experiencing drug shortages of epic proportion that are often associated with third-world countries. Respondents clearly believe the public is severely impacted by this issue, and several suggest that the problem has risen to the level of a national public health crisis.

By far, respondents were most alarmed by: the ever-increasing volume of critically important medications in short supply; the use of less desirable, often expensive, unfamiliar alternative drugs—if even available; the potential for errors and poor patient outcomes caused by absent or delayed treatment or preventable adverse drug events associated with alternative drugs or dosage forms; the lack of advanced warning about an impending shortage; and precious clinical hours lost to time-consuming activities required to manage drug shortages.

Frequency of drug shortage difficulties

During the past year, more than half of the respondents reported frequently or always encountering every one of the potential difficulties associated with drug shortages identified in our survey, which are listed in the next column in descending order starting with the most frequently encountered difficulty:

  • Little or no information available about the duration of a drug shortage (85%)
  • Lack of advanced warning from manufacturers or FDA to alert practitioners to an impending drug shortage and suggested alternatives (84%)
  • Little or no information about the cause of the drug shortage (83%)
  • Substantial resources spent investigating the shortage and developing a plan of action (82%)
  • Difficulty obtaining a suitable alternative product (80%)
  • Experience a significant financial impact (78%)
  • Lack of a suitable alternative product (70%)
  • Substantial resources spent preparing and/or administering the alternative products (69%)
  • Risk of adverse patient outcomes (64%)
  • Internal hoarding of medications associated with impending shortages (58%)
  • Physician anger towards pharmacists/nurses/hospital in response to a drug shortage (55%).

Physicians and pharmacists, particularly pharmacy managers and directors, reported encountering the above-listed problems more frequently than nurses, especially in areas such as spending resources to investigate shortages, developing a plan of action, hoarding medications in short supply, obtaining a suitable alternative, and experiencing the financial impact of purchasing drugs off contract or through secondary markets, or higher rushed delivery costs. While all professional disciplines clearly reported grave concerns regarding the risk of adverse patient outcomes during drug shortages, physicians reported encountering this risk more frequently than others, preceded in frequency only by lack of information about the causes and duration of shortages and lack of advanced warning from manufacturers or FDA.

Near misses, errors, adverse outcomes

Approximately one in three (35%) respondents reported that their facility had experienced a near miss during the past year due to a drug shortage. About one in four reported actual errors and one in five reported adverse patient outcomes during the past year due to drug shortages. More staff level practitioners (21%) reported adverse patient outcomes than administrative staff or directors/managers (18%), and as many as one in three (33%) physicians reported an adverse outcome caused by drug shortages this past year, more than pharmacists (21%) or nurses (16%). However, many respondents repeatedly commented that errors and adverse patient outcomes were not shared with them on a routine basis, were based on sporadic voluntary reporting, or were difficult to quantify. Thus, many felt the frequency of errors and adverse outcomes due to drug shortages is much greater than reported, and that not being aware of events did not mean they were not happening.

Respondents provided disquieting details regarding actual near misses, errors, and adverse patient outcomes associated with more than 50 drugs that had abruptly become unavailable, often without adequate notice. Table 1 provides just a glimpse at the many—more than 1,000!—near misses, errors, and adverse outcomes reported by respondents that occurred during the past year due to drug shortages. Especially troubling is that many of the drugs involved in the shortages are high-alert medications, such as propofol, heparin, epinephrine, morphine, neuromuscular blocking agents, chemotherapy, 50% dextrose, and parenteral electrolyte supplements; if not a high-alert medication, many other drugs in short supply are essential and lifesaving, such as antibiotics, IV fat emulsion, and fosphenytoin. 

Lack of alternative medications

Some drug shortages result in situations where a viable alternative is not available. For example, according to respondents, the shortage of amikacin and acyclovir has contributed to patient deaths from infections that were only sensitive to amikacin or treatable with acyclovir. Alternative antibiotics and antiviral medications were of little help in these situations. The shortage of various chemotherapeutic agents and adjunct therapy is another prime example. One respondent reported that stem cell transplantations were on hold because etoposide is not available. Another respondent said that important investigational drug studies have been put on hold because an adequate supply of adjunct medications required in the protocol could not be assured. Some hospitals and outpatient surgical centers have been forced to postpone surgeries indefinitely due to shortages of propofol and neuromuscular blocking agents; some have transferred patients to facilities that still have a supply of these crucial medications.

Issues with alternative medications

In other cases, alternative drugs or dosage forms/strengths are available when a drug shortage occurs, although the purchase price is often high. But even when alternatives can be identified, three serious problems were repeatedly voiced by survey respondents.

First, an alternative medication is often just that: an alternative to a drug with superior efficacy and/or a lower risk profile. For example, according to our survey respondents, alternative agents used in place of propofol for deep sedation have resulted in higher incidences of agitation and self-extubation in ventilated patients, and postoperative nausea and vomiting (related to the sedative, not analgesics) in surgical patients, which often led to extended hospitalization. To cite another example, an alternative medication may pose greater risk to patients with renal impairment than the drug in short supply. Certain diseases and conditions can be compromised when alternative products produce less than optimal treatment outcomes. In some instances, patients have allergies or a history of adverse reactions to the alternative medication and are left without an effective treatment option.

The next issue survey respondents raised is that the supply of alternative products can quickly become exhausted, leading to a secondary shortage of the alternative medication. For example, supplies of HYDROmorphone, a commonly used alternative during the morphine shortage, have become increasingly more difficult to obtain, particularly lower dose unit-of-use HYDROmorphone syringes. Thus, HYDROmorphone injection now joins morphine injection on the drug shortage list. The demand for an alternative drug may outpace the current supply, and companies that manufacture the product may not be prepared to address the sudden increased demand. The practice of hoarding drugs and viable alternatives in short supply by facilities places further demand on manufacturers.     

The third pressing issue raised by respondents is the risk of an error or adverse outcome when being asked to use unfamiliar alternative drugs. What is the correct dosage range and dosing frequency of the alternative drug? How is it prepared, stored, and administered? Are there untoward side effects that require patient monitoring? With so many drugs in short supply, several respondents admitted to increasing difficulty in just remembering which products are involved and what the suitable alternatives are—let alone how to safely prescribe, prepare, dispense, and administer the alternative drugs.

Physicians are asked to prescribe unfamiliar alternative drugs on the spot when called about an order for a drug in short supply; pharmacists are asked to safely dispense alternative medications, which often require additional unplanned time to prepare; nurses report that they never know what to expect when gathering medications. Will it be hydromorphone 1 mg/mL syringes in the automated dispensing cabinet? 2 mg/mL syringes? A 10 mg/mL vial? Will a totally different drug be required as an alternative? One nurse respondent stated, “I have lost count of how many times I have caught or witnessed another nurse catch a dosing error associated with hydromorphone since we never know what to expect.”

Respondents also touched upon the ethical dilemma they face when trying to prioritize use of any remaining stock of drugs involved in a shortage. Who gets the desirable medication, and who gets what may be a less desirable alternative drug? The stress of making such decisions can be seen in the brutally honest and emotional responses from the survey participants. As noted by one respondent, when a suitable alternative for a lifesaving drug is no longer available, “I guess patients just have to die.” Another respondent asked, “What do I tell our breast and lymphoma patients? You had a curable disease but not anymore because there is no drug available?”

Lack of notification about shortages

Respondents expressed significant concern regarding the lack of prior notification regarding an impending drug shortage. Most pharmacists (40%) and pharmacy technicians (51%) learn about a drug shortage the hard way—when the pharmacy department fails to receive an ordered product from a wholesaler or manufacturer. The next most frequently cited sources (24-32%) for learning about shortages included internal purchasing staff, word of mouth from other hospitals or professional listserves, secondary market contacts, and the American Society of Health-System Pharmacists (ASHP) website. Some respondents told us they often feel the impact of the shortage before it is officially communicated as a shortage.

Very few (6-15%) pharmacists, pharmacy technicians, nurses, and physicians rely on the FDA website or an advanced notice from a wholesaler, distributor, buying group, or drug manufacturer to learn about drug shortages. Among these entities, practitioners found the buying groups and wholesaler/distributors more helpful than FDA and the manufacturer. Some respondents suggested that drug manufacturers and distributors intentionally withhold information about an impending shortage until the last moment to prevent hoarding. This delay poses a significant threat to safety because practitioners have little time to prepare for the shortage.

Half of the physicians (50%) reported learning about drug shortages from pharmacists who call them after they have prescribed a drug in short supply, or from colleagues and the literature. Likewise, most nurses (52%) told us they learn about drug shortages primarily from the pharmacy department staff or unit manager; about 30% first learn about a drug shortage when pharmacy fails to dispense a prescribed medication.

Respondents also expressed their frustrations with drug companies that fail to disclose the cause of the shortage and underestimate how long the shortage will last. The disparity between information provided by drug companies and actual resolution of the shortage was called “unacceptable” by many.

Problems with secondary markets

Respondents voiced a growing concern that secondary markets (often called gray or black markets) seem to be able to gain access to drugs that are no longer available to healthcare providers through usual sources. These secondary markets contact pharmacists to advertise availability of scarce drugs, often at exorbitant prices. Some pharmacists expressed worry about the quality of products from secondary sources and felt that the exorbitant prices breach ethical lines, particularly when the drug in short supply is an essential lifesaving medication. Further conflict between healthcare providers and drug companies arises from what appears to be allowing select groups of individuals to still have access the drug or to be given a preferential warning about impending shortages so they can stockpile the drugs.

Next steps

The impact of drug shortages has taken an enormous toll on healthcare providers who are responsible for dealing with the problem, and the patients who are on the receiving end of the shortage. The man-hours alone spent on planning for the shortage, educating staff, restocking and coding the alternative products, dealing with secondary market vendors, and fielding calls from healthcare practitioners consumes a large portion of the pharmacists’ time, stealing valuable resources from clinical activities. Some respondents believe a full-time position will be needed in the future to manage drug shortages if the situation does not improve. Overall, survey respondents conveyed a real sense of crisis and are clearly looking for external support to reduce the burden and harm associated with drug shortages.

As mentioned in our article Drug shortages threaten patient safety, in our July 29, 2010 issue, ISMP and ASHP are interested in co-convening a public meeting with FDA and other key stakeholders representing the pharmaceutical industry, healthcare practitioners, regulatory authorities, and medication safety experts to explore and articulate the scope of this problem, and to develop a plan to reduce the occurrence of drug shortages and better manage them when they occur. More effective FDA oversight, a comprehensive early warning system, and patient safety and outcomes placed ahead of anyone’s profit margins are goals we hope to begin to explore at this meeting. ISMP and ASHP will keep readers apprised of progress to this end. Meanwhile, in a subsequent newsletter, we plan to provide guidelines for managing drug shortages on a local level within healthcare organizations.

Table 1. Examples of Near Misses, Errors and Adverse Outcomes Associated with Drug Shortages


  • Unintended intraoperative awareness occurred when a patient was given too little propofol based on weight in an attempt to conserve supplies
  • Misprogrammed PRECEDEX (dexmedetomidine) concentration in a smart pump; the drug was not in the library because it had never been used before the propofol shortage; the patient received a 20-fold overdose for 5 hours
  • Physician unfamiliar with Precedex dosed the drug in mcg/kg/minute instead of mcg/kg/hour
  • Infused VERSED (midazolam) at usual propofol rate; entire bag infused within a few hours, leading to oversedation
  • A paralyzed, ventilated patient received no sedation because propofol was not available and an alternative drug was never prescribed
  • Prolonged hospitalization from intractable post-op nausea and vomiting has occurred with alternative sedation agents
  • Difficulty extubating patients due to residual effects of ATIVAN (LORazepam)
  • Patients developed phlebitis and other known adverse reactions when etomidate was used in place of propofol
  • Respiratory spasms and airway obstruction required conversion to general anesthesia when alternative agents were used for sedation
  • Inadequate sedation with benzodiazepines led to agitation and self-extubation; one patient bit through her tongue
  • Difficulty weaning patients from the ventilator when using alternative sedation
  • Unnecessary use of general anesthesia for procedures that could be performed with deep sedation

Neuromuscular Blocking Agents

  • Compounded syringes of vecuronium and succinylcholine from the same company looked similar; auxiliary labels for vecuronium accidentally applied to succinylcholine, leading to a mix-up
  • Infused rocuronium at the rate intended for cisatracurium
  • Administered pancuronium to patient with renal failure, which resulted in excessive and prolonged paralysis and tachycardia
  • Patient given the wrong dose of a neuromuscular blocking agent when the anesthesia provider forgot that an alternative drug was being used
  • Patient received the wrong dose of succinylcholine after an alternative concentration of the drug was provided
  • Several patients receiving rocuronium got the wrong dose because the physician dosed it in mcg/kg/hour, not mcg/kg/minute
  • Wrong dose of vecuronium calculated using a written protocol intended for pancuronium
  • Early self-extubation due to shorter duration with alternative neuromuscular blocking agents
  • Cancellations of surgeries and procedures
  • Two patients developed possible rocuronium-induced pulmonary hypertension when preferred agents, cisatracurium and vecuronium, were unavailable


  • IV HYDROmorphone prescribed at the intended dose for morphine and administered, resulting in the death of two patients
  • HYDROmorphone 0.5 mg IV was supposed to be substituted for morphine 4 mg IV, but HYDROmorphone 4 mg IV was given in error
  • Administered 4 mg of morphine IV believing the vial held 2 mg
  • Administered 8 mg of morphine IV instead of 2 mg; only 8 mg syringes available from manufacturer
  • Administered 10 mg (10 mg/mL) of morphine instead of 1 mg (1 mg/mL); patient required naloxone and was transferred to critical care
  • Misfilled an automated dispensing cabinet (ADC) pocket for 2 mg morphine vials with 10 mg morphine vials
  • Patient switched from morphine 6 mg IV to HYDROmorphone without changing the dose; patient received several 6 mg doses, which required naloxone administration and increased the length of hospitalization
  • Wrong dose of morphine administered after 4 mg/mL prefilled syringes were replaced with 5 mg/mL vials; bar-coding system overridden due to the emergent switch in strengths, which had not yet been entered into the bar-coding system
  • Increased incidence of drug diversion because pharmacy-prepared syringes of morphine and HYDROmorphone are less tamper-resistant than commercially available syringes


  • Unable to keep up with the demand for EPINEPHrine doses during a code, as each 1:1,000 ampul needed to be diluted; patient died 10-fold overdose of EPINEPHrine administered when nurse withdrew 10 mL of a 1:1,000 solution, assuming the vial contained a 1:10,000 solution
  • During EPINEPHrine shortage, 30 mL vials of topical EPINEPHrine were ordered by mistake and loaded into crash carts; the wrong product was reordered from the same order label several times
  • In crash carts, EPINEPHrine Bristojects were replaced with an EPINEPHrine syringe with a permanently attached intra-cardiac needle; during a code, a nurse jammed the cardiac needle through a needleless system port, which broke the valve; the tubing had to be changed during the code
  • EPINEPHrine with an intra-cardiac needle was needed but not available during a code; the cart had been stocked with EPINEPHrine 1:10,000 prefilled syringes (no cardiac needle) from a compounding company
  • An EPINEPHrine 1:1,000 (1 mg/mL) ampul was removed from an ADC; nurse administered the entire ampul IV along with other IV medications but should have administered 0.3 mg IM; patient developed tachycardia and elevated troponin levels necessitating transfer to another hospital
  • A patient failed to respond during a code after a nurse accidentally administered a pediatric emergency dose of EPINEPHrine, although the cart was stocked with EPINEPHrine 1:1,000 vials, diluent, and instructions for dilution
  • Pharmacy had been preparing 10 mL syringes of EPINEPHrine 1:10,000 (0.1 mg/mL) and atropine (1 mg/mL); nurse grabbed atropine by mistake and administered it during a code instead of the intended EPINEPHrine


  • A nurse prepared and administered an incorrect strength of heparin infusion (30,000 units/500 mL) when the pharmacy was closed at night
  • Heparin bags prepared in the pharmacy look similar to other pharmacy admixtures; heparin was administered over 90 minutes instead of vancomycin, and azithromycin was administered instead of heparin
  • Prescribers who switched from IV heparin to subcutaneous enoxaparin initially prescribed the wrong dose and frequency of administration
  • Vials containing the wrong strength of heparin were stocked in an ADC, leading to dosing errors
  • Hoarded bags of heparin were stored in the hospital's distribution center to save space in the pharmacy, where they were accidentally dispensed to a nursing unit instead of plain IV solutions
  • IV heparin was administered instead of magnesium during a code because the 10,000 units/mL heparin vials purchased to replace the 5,000 units/mL vials looked similar to magnesium vials
  • A pharmacy-prepared heparin infusion containing 25,000 units/500 mL (50 units/mL) was accidentally dispensed to the NICU and administered for 2 hours instead of the intended pharmacy-prepared solution containing 0.5 units/mL


  • Phenytoin dispensed in place of fosphenytoin was administered IV into a peripheral vein too rapidly, which resulted in severe thrombophlebitis in a pediatric patient
  • Phenytoin, which was reintroduced into the OR because of the fosphenytoin shortage, was administered IV too rapidly during surgery, which resulted in an arrhythmia and cardiac arrest
  • Nurse programmed IV phenytoin to infuse over 2 hours instead of 1 hour (as noted on the pharmacy label due to stability issues), which caused several ports to clog; the patient required surgery to implant a new long-term central line, which delayed hematopoietic stem cell transplantation (HSCT) conditioning


  • Cytarabine dosing error occurred when a pharmacist used a mixing protocol applicable to the usual 500 mg vials (50 mg/mL, not available) but was actually using an alternative strength 1,000 mg vial
  • Pre-diluted methotrexate was unavailable; a vial of dry powder was reconstituted incorrectly and the patient received less than the prescribed dose
  • VinBLAStine shortage led to replacement with vinCRIStine for a patient with a hematologic disease, but a dosing error occurred when determining the dose for the alternative drug
  • IV etoposide was converted to oral dosing, but the prescriber was not aware that the oral dose needed to be double the IV dose
  • Physician prescribed the wrong dose when levoleucovorin was substituted for leucovorin
  • Chemotherapy treatments delayed in a patient with a high potential for remission while attempting to find a source of the needed drug
  • Switched cancer patients from leucovorin to levoleucovorin, from fluorouracil to capecitabine, and from asparaginase to pegasparagase, but the impact on overall survival and quality of life is undetermined
  • Substituting XELODA (capecitabine) for leucovorin has resulted in serious gastrointestinal toxicity in many patients
  • Chemoembolization was significantly delayed due to unavailability of mitomycin


  • A patient with a pseudomonas infection sensitive only to amikacin died when the drug could not be provided
  • Inability to treat with amikacin in a patient with established resistance caused readmission due to treatment failure with ineffective alternatives
  • A patient with viral meningitis had to be transported by helicopter from one hospital to another because IV acyclovir was not available, which increased the patient's length of hospitalization
  • A patient with probable meningitis experienced a clinically significant delay in therapy while awaiting an alternative antiviral agent; the limited stock of IV acyclovir was sequestered for use in the NICU, where alternative therapies are limited
  • Shortage of IV BACTRIM (sulfamethoxazole and trimethoprim) led to refractory cases of PCP (pneumocystis pneumonia) from alternative treatment with clindamycin and primaquine
  • Clinically significant delay in treating a patient with PCP due to IV Bactrim shortage, particularly when alternatives were not available either; the patient required transfer to another hospital that had enough IV Bactrim to treat the patient


  • Treatment delays in hypoglycemic patients when dextrose 50% vials could not be located in an ADC, when pharmacy-prepared mini-bags stocked in the refrigerator could not be located, and when a nurse could not locate a 60 mL syringe and a large-bore needle to withdraw the dextrose from vials 
  • Patients on flunisolide had to be converted to mometasone; one patient was already on mometasone due to an adverse drug reaction with flunisolide; when flunisolide became available again, the patient was inadvertently converted to flunisolide
  • Prefilled ondansetron syringes became unavailable necessitating use of 4 mg/mL vials, which look like hydrALAZINE vials; hydrALAZINE was accidentally stocked in an ondansetron bin and dispensed to a patient care unit
  • Patient deteriorated after only receiving partial doses of imiglucerase due to rationing of the drug
  • Hospital recently converted from IV indomethacin to IV ibuprofen because of better safety profile; after ibuprofen recall, neonate required the drug to treat a patent ductus arteriosus; neonate given indomethacin as an alternative but developed a gastrointestinal perforation associated with indomethacin treatment



  1. ISMP. ISMP survey on drug shortages. ISMP Medication Safety Alert! 2010;15(15):4.