Introduction
Medications are compounded when a formulation of a medication is needed but not commercially available. Regulatory oversight of compounding is piecemeal and compounding errors have resulted in patient harm. We review compounding in the United States (US), including a history of compounding, a critique of current regulatory oversight, and a systematic review of compounding errors recorded in the literature.
Methods
We gathered reports of compounding errors occurring in the US from 1990 to 2020 from PubMed, Embase, several relevant conference abstracts, and the US Food and Drug Administration “Drug Alerts and Statements” repository. We categorized reports into errors of “contamination,” suprapotency,” and “subpotency.” Errors were also subdivided by whether they resulted in morbidity and mortality. We reported demographic, medication, and outcome data where available.
Results
We screened 2155 reports and identified 63 errors. Twenty-one of 63 were errors of concentration, harming 36 patients. Twenty-seven of 63 were contamination errors, harming 1119 patients. Fifteen errors did not result in any identified harm.
Discussion
Compounding errors are attributed to contamination or concentration. Concentration errors predominantly result from compounding a prescription for a single patient, and disproportionately affect children. Contamination errors largely occur during bulk distribution of compounded medications for parenteral use, and affect more patients. The burden falls on the government, pharmacy industry, and medical providers to reduce the risk of patient harm caused by compounding errors.
Conclusion
In the US, drug compounding is important in ensuring access to vital medications, but has the potential to cause patient harm without adequate safeguards.
Direct oral anticoagulants are now commonplace, and reversal agents are recently becoming available. Andexanet alfa (AnXa), approved by the United States Food and Drug Administration in 2018, is a novel decoy molecule that reverses factor Xa inhibitors in patients with major hemorrhage. We present a case of a 70-year-old man taking rivaroxaban with hemodynamic instability from a ruptured abdominal aortic aneurysm. He received AnXa prior to endovascular surgery, and intraoperatively he could not be heparinized for graft placement. Consideration should be given to the risks and benefits of AnXa administration in patients who require anticoagulation after hemorrhage has been controlled.
The COVID-19 pandemic has triggered outbreaks of unanticipated toxicities, including methanol toxicity. Multiple methanol outbreaks have been described, including contaminated hand sanitizer in the southwest USA. In this case, we describe a fatal case of methanol toxicity from hand sanitizer ingestion, geographically separated from the outbreak in the southwest USA and prior to the announcement of nationwide warnings by the Food and Drug Administration (FDA). The product was identified as one later recalled by the FDA for methanol contamination. Additionally, the consumption in this case was related to a desire to conceal alcohol consumption from family members. This case of methanol toxicity should increase awareness of the ease of which contaminated products can be widely distributed and of the use of alternative ethanol-containing products to obscure relapse in alcohol use disorder.
The rules of fair play in sport generally prohibit the use of performance-enhancing drugs (PEDs). The World Anti-Doping Agency (WADA) oversees global antidoping regulations and testing for elite athletes participating in Olympic sports. Efforts to enforce antidoping policies are complicated by the diverse and evolving compounds and strategies employed by athletes to gain a competitive edge. Now between the uniquely proximate 2021 Tokyo and 2022 Beijing Olympic Games, we discuss WADA's efforts to prevent PED use during the modern Olympic Games. Then, we review the major PED classes with a focus on pathophysiology, complexities of antidoping testing, and relevant toxicities. Providers from diverse practice environments are likely to care for patients using PEDs for a variety of reasons and levels of sport; these providers should be aware of common PED classes and their risks.
BackgroundWhen ingested by children, small quantities of beta‐adrenergic antagonists (BAA) are described as dangerous and even potentially lethal (“one pill can kill”). We characterize demographics, clinical characteristics, and the rate of serious outcomes among pediatric patients with reported BAA ingestions.MethodsThis study was a retrospective review of U.S. patients <20 years old with reported single‐agent BAA ingestions presenting to a health care facility between January 2000 and February 2020 for whom a poison control center was consulted. Data were abstracted from the National Poison Data System (NPDS). Medical outcomes were assessed by the NPDS scale of no effect, minor effect, moderate effect, major effect, and death. All relevant NPDS fatality narratives were reviewed.ResultsA total of 35,436 reported exposures were identified. A total of 29,155 (82.3%) were <6 years old, of which 29,089 (99.8%) were unintentional. Twenty‐five patients (<0.1%) <6 years old had major effects. A total of 2316 (8.8%) of patients with no/mild effects were admitted to a critical care unit. Of all cases, 1460 (4.1%) had hypotension and 1403 (4.0%) had bradycardia. One hundred nineteen (0.3%) developed hypoglycemia. The only four fatalities resulted from intentional ingestions in patients >10 years old who sustained cardiac arrest in the prehospital setting.ConclusionsReported BAA ingestions in this multiyear national pediatric cohort caused infrequent toxicity, and no fatalities resulted from an unintentional ingestion. The frequency of bradycardia, hypotension, and hypoglycemia were low. While severely poisoned patients require aggressive treatment, 8.8% of patients were admitted to a critical care unit despite having no or mild effects, which suggests an opportunity to reduce resource utilization.
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