Shortages of agents used to treat antimuscarinic delirium.

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. 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. 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. 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.

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Declaration of Competing Interest This work has no source of funding. Maryann Mazer-Amirshahi, Kieran Glowacki, Pelayia Soto, and James Whitledge have no financial benefits or conflicts of interest to disclose. Erin Fox leads the University of Utah Drug Information Service (UUDIS). The UUDIS has a contract with Vizient (a GPO) to provide drug shortage information. The total amount represents less than 5% of the UUDIS budget. No funds are paid directly to Erin Fox. Erin Fox receives partial travel support for providing continuing education on drug shortages from the Drug Information Association. We certify that our submission is original and not under review by any other journal. All authors meet the criteria for authorship stated in the Uniform Requirements for Manuscripts Submitted to Biomedical Journals, and all listed authors have read and approve this submission.