Trends in Shortages of Lead Chelators From 2001 to 2022.

OBJECTIVE: The study aims to describe drug shortages affecting lead chelators in the United States from 2001 through 2022. METHODS: Drug shortage data were retrieved from the University of Utah Drug Information Service from January 1, 2001, through December 31, 2022. Shortages of first- and second-line lead chelators were analyzed. Drug class, formulation, administration route, shortage reason, shortage duration, generic status, single-source status, and presence of temporally overlapping shortages were examined. Total shortage months, percentages of study period on shortage, and median shortage durations were calculated. RESULTS: Thirteen lead chelator shortages were reported during the study period. Median duration was 7.4 months and the longest shortage (24.8 months) involved calcium disodium edetate. Calcium disodium edetate and dimercaprol had the greatest number of shortages, 4 each, and 61.5% of shortages involved parenteral medications. Median shortage duration was 14.2 months for parenteral agents and 2.2 months for non-parenteral agents. All shortages involved generic, single-source products. Supply/demand and manufacturing problems were the most common shortage reasons provided. Overlapping shortages occurred for 3.7% of the study period. Median shortage duration increased from 3 to 11 months in the second half of the study period, and 61.5% of shortages occurred in the second half of the study period. CONCLUSIONS: All chelators experienced multiple shortages, which became increasingly frequent and prolonged over time. Concurrent shortages occurred, potentially hampering substitution between different agents. Health care stakeholders must build supply chain resilience and develop guidelines regarding how to modify chelation therapy based on shortage conditions.

The empty code cart: Drug shortages over time.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: In high-acuity situations such as cardiac arrest, clinicians rely on prepared medications stocked in code carts to provide timely and accurate pharmacotherapy. We examined shortage trends for medications commonly used in code carts. METHODS: Drug shortage data from 2001 to 2022 were retrieved from the University of Utah Drug Information Service (UUDIS) to characterize shortages reported for commonly used code cart medications. Data extracted included the number of shortages, shortage duration, drug characteristics, and reason for the shortage. RESULTS: From 2001 to 2022, 71 drug shortages for code cart medications were reported. The number of new shortages peaked in 2010, and the number of total shortages peaked in 2010. At the end of the study period, 61 (84.7%) shortages had been resolved. For resolved shortages, the mean shortage duration was 18.2 months. The drug with the greatest number of reported shortages was dextrose (10 total), the drug with the longest resolved shortage was calcium chloride injection (116 months), and the drug with the longest active shortage was atropine injection (165 months at the end of the study period). Throughout the entire study period, only 2 suppliers provided commercially available prefilled syringes of dextrose for stocking on code carts. The most common reason for shortages, when reported, was manufacturing delays. CONCLUSION: Medications commonly used in code carts were frequently impacted by drug shortages, which have the potential to impact patient care. Institutional protocols for mitigation and larger efforts to promote a more resilient drug supply chain are critical to ensure patient safety and quality care.

Evaluation of pharmacy-supplied half and quarter tablets at an academic medical center.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: Manipulation of tablet medications to produce a customized dose is common practice, and splitting tablets may reduce the acquisition cost of the medication. However, cost savings may be diminished by the cost of the increased labor and repackaging materials needed when splitting tablets. Splitting tablets may also result in safety concerns if the final products are under (eg, reduced benefit) or over (eg, toxicity) the desired dosage. The purpose of this quality improvement project was to evaluate and recommend changes for all half- and quarter-tablet medications prepared and distributed from the inpatient pharmacy at University of Utah Health (U of U Health). SUMMARY: The evaluation included all half- and quarter-tablet medications prepared by pharmacy technicians for administration to patients admitted to U of U Health hospitals. A final list of 173 half- and quarter-tablet dosages was evaluated for opportunities to decrease the total number. On the basis of the developed criteria, 93 half- and quarter-tablet dosages (54%) were recommended to be removed from routine stock in the inpatient pharmacy. Systems remain in place to create customized half and quarter tablets if required for patient care. CONCLUSION: Reducing the number of medications for which half and quarter tablets are used may allow pharmacy technicians to prioritize other patient care tasks and potentially decrease waste.

How Should Critical Medications Be Rationed During Shortages?

When any drug is in short supply, it must be rationed. Recent increases in the frequency of shortages require more rationing by clinicians. Most health systems have policies on managing drug shortages, but transparency of criteria according to which specific scarce medications should be rationed-and by whom-are rare. The COVID-19 pandemic offered several examples of clinical and ethical need to develop and implement clear, fair strategies for distributing medications in short supply. Lessons from the pandemic should inform strategies for managing drug shortages now and in the future.

Shortages of agents used to treat antimuscarinic delirium.

INTRODUCTION: Antimuscarinic delirium (AD), a potentially life-threatening condition frequently encountered by emergency physicians, results from poisoning with antimuscarinic agents. Treatment with physostigmine and benzodiazepines is the mainstay of pharmacotherapy, and use of dexmedetomidine and non-physostigmine centrally-acting acetylcholinesterase inhibitors (cAChEi) such as rivastigmine has also been described. Unfortunately, these medications are subject to drug shortages which negatively impact the ability to provide appropriate pharmacologic treatment of patients with AD. METHODS: Drug shortage data were retrieved from the University of Utah Drug Information Service (UUDIS) database from January 2001 through December 2021. Shortages of first-line agents used to treat AD (physostigmine and parenteral benzodiazepines) and second-line agents (dexmedetomidine and non-physostigmine cAChEi) were examined. Drug class, formulation, route of administration, reason for shortage, shortage duration, generic status, and whether the drug was a single-source product (made by only one manufacturer) were extracted. Shortage overlap and median shortage durations were calculated. RESULTS: Twenty-six shortages impacting drugs used to treat AD were reported to UUDIS from January 1, 2001 to December 31, 2021. Median shortage duration for all medication classes was 6.0 months. Four shortages were unresolved at the end of the study period. The single medication most often on shortage was dexmedetomidine, however benzodiazepines were the most common medication class on shortage. Twenty-five shortages involved parenteral formulations, and one shortage involved the transdermal patch formulation of rivastigmine. The majority (88.5%) of shortages involved generic medications, and 50% of products on shortage were single-source. The most common reported reason for shortage was a manufacturing issue (27%). Shortages were often prolonged and, in 92% of cases, overlapped temporally with other shortages. Shortage frequency and duration increased during the second half of the study period. CONCLUSION: Shortages of agents used in the treatment of AD were common during the study period and affected all agent classes. Shortages were often prolonged and multiple shortages were ongoing at study period end. Multiple concurrent shortages involving different agents occurred, which could hamper substitution as a means of mitigating shortage. Healthcare stakeholders must develop innovative patient- and institution-specific solutions in times of shortage and work to build resilience into the medical product supply chain to minimize future shortages of drugs used for treatment of AD.

Development of a proactive process to harmonize policy, infusion pump library, and electronic health record entries for continuous infusions at an academic medical center.

PURPOSE: Standardized processes to order and prepare medications can decrease the potential for error and provider uncertainty. Our health system utilizes a standard concentration policy, smart infusion pumps, and the electronic health record (EHR) to catalog, order, and deliver intravenous medications. A need for a more proactive and formalized process to ensure medication listings are harmonized between these 3 resources was identified. Standardizing these resources can reduce confusion, reduce time spent in pharmacy operations and nursing workflow, and may improve patient safety. The purpose of this quality improvement project was to compare and resolve inconsistencies between these 3 sources and to create a new process to assure uniformity in a complex work environment. SUMMARY: An audit-style comparison and evaluation of entries for continuous infusions within the standard concentration policy, the pump library, and the EHR was conducted. All continuous infusion entries within any one of these 3 sources were included. Key exclusion criteria included pediatric and neonatal infusions, intermittent infusions, and infusions in procedural areas. We compared the policy, the pump library, and the EHR to identify, document, and resolve discrepancies in medication name, concentration, rate, and volume; fluid restriction concentration; and upper and lower pump limits. A new method to ensure proactive continuity and consistent updates to the 3 sources was implemented into existing operational workflows. We recommended a total of 82 updates to policy (n = 48), the pump library (n = 30), and the EHR (n = 4) out of 187 continuous infusion entries. CONCLUSION: Standardizing infusion resources will reduce confusion, and improve pharmacy operations, nursing workflow, and patient safety.

A data-driven quality-score system for rating drug products and its implications for the health care industry.

The quality of drug products in the United States has been a matter of growing concern. Buyers and payers of pharmaceuticals have limited insight into measures of drug-product quality. Therefore, a quality-score system driven by data collection is proposed to differentiate between the qualities of drug products produced by different manufacturers. The quality scores derived using this proposed system would be based upon public regulatory data and independently-derived chemical data. A workflow for integrating the system into procurement decisions within health care organizations is also suggested. The implementation of such a quality-score system would benefit health care organizations by including the consideration of the quality of products while also considering price as a part of the drug procurement process. Such a system would also benefit the U.S. health care industry by bringing accountability and transparency into the drug supply chain and incentivizing manufacturers to place an increased emphasis on the quality and safety of their drug products.

US drug shortages compared to the World Health Organization's Model List of Essential Medicines for Children: A cross-sectional study.

PURPOSE: To describe US drug shortages affecting medications on the 2019 World Health Organization (WHO) Model List of Essential Medicines for Children (EMLc). METHODS: Drug shortage data from January 2014 to December 2019 were obtained from the University of Utah Drug Information Service. Shortage data for drugs on the EMLc were analyzed for the type of drug, American Hospital Formulary Service category, reason for the shortage, duration of the shortage, marketing status (generic vs brand name), and whether the agent was a single- or multisource drug. RESULTS: From 2014 to 2019, a total of 209 drug shortages impacted medications on the EMLc, of which 77 (36.8%) remained unresolved by 2019. Of all active shortages, 13 (6.2%) began before 2014. Resolved shortages had a median duration of 5.9 months (interquartile range [IQR], 3.6-13.2 months) while active shortages had a median duration of 18.3 months (IQR, 10.9-33.5 months; P ≤ 0.0001). The therapeutic categories most impacted by drug shortages were anti-infective agents (27.3%), central nervous system agents (12.9%), and antineoplastic agents (11.0%). The reason for the shortage was not reported in 46.4% of cases. When a reason was provided, the most common reason was manufacturing problems (29.2%) followed by supply/demand mismatch (15.8%). CONCLUSION: US drug shortages affected many medications on the WHO EMLc. Future studies should examine the global shortage climate and implications for patient care.

A 2019 evaluation of opioid use disorder treatment resources in rural Utah counties.

OBJECTIVES: The opioid crisis significantly affects residents of rural communities who already experience poor health outcomes based on social determinants. Therefore, this project evaluated the reported availability and accessibility of opioid use disorder (OUD) treatment resources in rural Utah county pharmacies through a multistep process intended to estimate the distance (miles) to registered (waivered) OUD care providers and community pharmacies and, thus, the ability to fill prescriptions for OUD treatment medications. METHODS: First, the United States Department of Agriculture Economic Research Service dichotomous classification scheme was used to identify nonmetropolitan counties. Second, online resources were used to identify the volume of waivered treatment providers and community pharmacies by county. Third, the driving distances to both resources were estimated according to ZIP Code and county. Finally, the immediate availability of filling a prescription for OUD treatment medications was determined by surveying community pharmacists in rural Utah counties. RESULTS: Nineteen of the 29 Utah counties were identified as rural and included in the study. Pharmacists in 50 of the 75 viable pharmacies completed surveys (66.7% usable response rate). OUD treatment medications were immediately available for dispensing in 90% (45 of 50) of the responding pharmacies. Two of the 19 counties (10.5%) lacked a pharmacy, and 6 of the 19 counties (31.6%) lacked a registered OUD treatment provider. Driving distances ranged from 1 mile to 71 miles to the nearest pharmacy and from 1 mile to 96 miles to the nearest waivered treatment provider. CONCLUSION: OUD treatment medications were readily available in some but not all rural Utah pharmacies. However, geographic barriers may prevent reasonable access to treatment providers and pharmacies for residents of smaller, remote communities.

The Impact of the Parenteral Opioid Medication Shortages on Opioid Utilization Practices in the Emergency Department of Two University Hospitals.

INTRODUCTION: Both opioid and non-opioid analgesics are commonly utilized in treating acute and chronic pain in the emergency department (ED). Opioid stewardship efforts have focused on judicious opioid use and opioid alternatives as first-line analgesics. Parenteral opioid formulations have been impacted by periodic shortages creating the opportunity for a natural experiment to observe how emergency clinician prescribing behavior may be impacted. We investigated the change in analgesic practice related to a period of parenteral opioid shortage at two large urban, academic medical centers. METHODS: A retrospective review of pharmacy administration data from two academic urban EDs was performed looking at time periods before, during, and after resolution of the parenteral opioid shortage. The data were analyzed by medication, dose, time, number of doses, and oral morphine milligram equivalents (MME) administered per patient. RESULTS: The percentage of patients who received any opioid among ED visits decreased during the shortage period and did not return to pre-shortage levels after the shortage ended: 11.5% pre, 8.5% during (p=0.01), 7.2% post (NS; p=0.18). The number of doses of either oral or IV opioid doses administered during the shortage decreased significantly: 8.7% pre, 5.6% during (p=0.02) for PO, and 13.7% pre, 9.0% during (p=0.004) for IV, and neither changed during recovery from the shortage. The percentage of patients receiving non-opioid analgesics rose from 30.5% before to 45.8% (p=0.004) after the shortage. Among patients who received opioids, the MME per patient did not change across the time periods: 11.5% before, 11.2% during, 12.7% post. CONCLUSIONS: A period of restricted opioid use due to parenteral opioid shortages led to less opioid use overall and fewer patients treated with opioids, yet no significant change in opioid MME administered per patient requiring opioids. Overall, the shift in opioid prescribing during the parenteral opioid shortage appeared to be sustained in the post-shortage period.

Developing statewide remdesivir use criteria.

PURPOSE: This report describes our process of 4 health systems coming together to agree on standard use criteria for remdesivir as a coronavirus disease 2019 (COVID-19) treatment for patients in Utah. We hope our process provides a framework for remdesivir use in other states and insights on future use of other therapeutic agents that may also be in short supply, such as vaccines and monoclonal antibodies. SUMMARY: Emergency use authorization (EUA) criteria for COVID-19 treatments often allow for broad use of a treatment relative to limited supplies. Without national criteria, each health system must develop further rationing criteria. Health systems in Utah worked together as part of the state's crisis standards of care workgroup to develop a framework for how to limit the EUA criteria for remdesivir to match available supplies. The 4 largest health systems were represented by infectious diseases specialists, chief medical officers, and pharmacists. The group met several times online and communicated via email over a 9-day period to develop the criteria. The clinicians agreed to use this framework to develop criteria for future therapeutics such as monoclonal antibodies. CONCLUSION: The unique collaboration of the 4 health systems in Utah led to statewide criteria for use of remdesivir for patients with COVID-19, ensuring similar access to this limited resource for all patients in Utah.

Prescription Drug Shortages: Pediatric Emergency and Critical Care Medications.

OBJECTIVES: Drug shortages have been increasing over the past 2 decades. There are limited data on drug shortages and their effect on pediatric emergency and critical care. Our objective was to describe pediatric emergency and critical care drug shortages. METHODS: Drug shortage data from January 2001 to December 2015 were obtained from the University of Utah Drug Information Services. Shortages were reviewed, identifying agents used in pediatric emergency and critical care. Shortage data were analyzed for the type of drug, formulation, shortage reason, duration, marketing status (generic vs brand name), or if it was a pediatric-friendly formulation, used for a high-acuity condition, or a single-source product. The availability of a substitute was also described. RESULTS: Of 1883 products on shortage, 779 were used in pediatric emergency or critical care. The annual number of shortages decreased from 2001 to 2004, but then increased, reaching a high in 2011. The median duration for resolved shortages was 7.6 months (interquartile range, 3.0-17.6 months). The most common category affected was infectious disease drugs. High-acuity agents were involved in 27% of shortages and in 11% of pediatric-friendly formulations. An alternative agent was available for 95% of drugs, yet 43% of alternatives were also affected at some time during the study period. The most common reported reason for a shortage was manufacturing problems. CONCLUSIONS: From 2001 to 2015, drug shortages affected a substantial number of agents used in pediatric emergency and critical care. This has had implications to the medications available for use and may impact patient outcomes. Providers must be aware of current shortages and implement mitigation strategies to optimize patient care.

The rising cost of commonly used emergency department medications (2006-15).

OBJECTIVE: We determine how aggregate costs have changed for commonly used emergency department (ED) medications, and assess drivers of cost increases. METHODS: Using the National Hospital Ambulatory Medical Care Survey (NHAMCS), we identified the top 150 ED medications administered and prescribed at discharge in 2015. We used average wholesale prices (AWP) for each year from 2006 to 15 from the Red Book (Truven Health Analytics Inc.). Average wholesale price per patient (AWPP) was calculated by dividing AWP by drug uses. This was then multiplied by the total drug administrations or prescriptions to estimate the total cost in a given the year. All prices were converted to 2015 dollars. RESULTS: Aggregate costs of drugs administered in the ED increased from $688.7 million in 2006 to $882.4 million in 2015. For discharge prescriptions, aggregate costs increased from $2.031 billion in 2006 to $4.572 billion in 2015. AWPP for drugs administered in the ED in 2015 was 14.5% higher than in 2006 and 24.3% higher at discharge. The largest absolute increase in AWPP for drugs administered was for glucagon, which increased from $111 in 2006 to $235 in 2015. The largest AWPP increase at discharge was for epinephrine auto-injector, which increased from $124 in 2006 and to $481 in 2015. CONCLUSION: Over the course of the study period, the aggregate costs of the most common medications administered in the ED increased by 28% while the costs of medications prescribed at discharge increased 125%.

COVID-19 and Drug Shortages: A Call to Action.

The ever-vulnerable medication supply chain is being further strained by the COVID-19 pandemic. Pharmacists in all settings, including managed care, will need to prepare for a potential exacerbation of existing and new drug shortages in the midst of unprecedented crisis. We summarize the major issues, discuss potential mitigation strategies, and call on our colleagues to respond with the resilience necessary to protect our patients. DISCLOSURES: The authors declare no funding sources nor conflicts of interest.