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.
The Toxicology Investigators Consortium (ToxIC) Core Registry was established by the American College of Medical Toxicology in 2010. The Core Registry collects data from participating sites with the agreement that all bedside and telehealth medical toxicology consultations will be entered. This twelfth annual report summarizes the registry’s 2021 data and activity with its additional 8552 cases. Cases were identified for inclusion in this report by a query of the ToxIC database for any case entered from January 1 to December 31, 2021. Detailed data was collected from these cases and aggregated to provide information, which included demographics, reason for medical toxicology evaluation, agent and agent class, clinical signs and symptoms, treatments and antidotes administered, mortality, and whether life support was withdrawn. Gender distribution included 50.4% of cases in females, 48.2% of cases in males, and 1.4% of cases in transgender or gender non-conforming individuals. Non-opioid analgesics were the most commonly reported agent class (14.9%), followed by opioids (13.1%). Acetaminophen was the most common agent reported. Fentanyl was the most common opioid reported and was responsible for the greatest number of fatalities. There were 120 fatalities, comprising 1.4% of all cases. Major trends in demographics and exposure characteristics remained similar to past years’ reports. Sub-analyses were conducted to describe new demographic characteristics, including marital status, housing status and military service, the continued COVID-19 pandemic and related toxicologic exposures, and novel substances of exposure.
Supplementary Information
The online version contains supplementary material available at 10.1007/s13181-022-00910-6.
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