Adverse Events Related to Accidental Unintentional Ingestions From Cough and Cold Medications in Children.

OBJECTIVES: Previous research has demonstrated that accidental unsupervised ingestions (AUIs) were responsible for the majority of cough and cold medication (CCM) ingestions leading to significant adverse events (AEs) in children. The objective of this analysis was to characterize the role of AUIs in the morbidity associated with CCM exposure in children. METHODS: This surveillance study collected data from 5 United States data sources from 2009 to 2016, in children younger than 6 years with an AE from an AUI involving at least 1 CCM over-the-counter pharmaceutical ingredient. An expert panel reviewed each case to determine causality. RESULTS: From 4756 total cases reviewed, 3134 (65.9%) had an AE from an AUI determined to be at least potentially related to a CCM ingredient. The majority (61.3%) of cases occurred in children aged 2 to younger than 4 years. Most exposures occurred in the child's own residence (94.9%), and 43.8% were admitted to a health care facility (22.0% to a critical care unit). Dextromethorphan and diphenhydramine, when packaged alone or in combination products, contributed to 96.0% of AUIs. The most common specific products involved were single-ingredient pediatric liquid diphenhydramine (30.1%) and single-ingredient pediatric liquid dextromethorphan (21.4%). There were 3 deaths from solid diphenhydramine formulations. CONCLUSIONS: There continues to be opportunities for the implementation of interventions to prevent AUIs of CCM in children. Additional emphasis on engineering controls, such as flow restrictors for liquid formulations targeting diphenhydramine and dextromethorphan products, represent additional opportunities to further reduce AEs from AUIs of CCM.

Pediatric Fatalities Associated With Over-the-Counter Cough and Cold Medications.

BACKGROUND AND OBJECTIVES: In 2008, over-the-counter cough and cold medications (CCMs) underwent labeling changes in response to safety concerns, including fatalities, reported in children exposed to CCMs. The objective of this study is to describe fatalities associated with exposures to CCMs in children <12 years old that were detected by a safety surveillance system from 2008 to 2016. METHODS: Fatalities in children <12 years old that occurred between 2008 and 2016 associated with oral exposure to one or more CCMs were identified by the Pediatric Cough and Cold Safety Surveillance System. An expert panel reviewed all cases to determine the causal relationship between the exposure and death, if the intent of exposure was therapeutic, and if the dose was supratherapeutic. Other contributing factors related to the child's death were also identified as part of a root cause analysis. RESULTS: Of the 180 eligible fatalities captured during the study period, 40 were judged by the expert panel to be either related or potentially related to the CCM. Of these, the majority (n = 24; 60.0%) occurred in children <2 years old and involved nontherapeutic intent (n = 22; 55.0%). The most frequently involved index ingredient was diphenhydramine (n = 28; 70.0%). In 6 cases (n = 6; 15.0%), the CCM was administered to murder the child. In another 7 cases (n = 7; 17.5%), death followed the intentional use of the CCM to sedate the child. CONCLUSIONS: Pediatric fatalities associated with CCMs occurred primarily in young children after deliberate medication administration with nontherapeutic intent by a caregiver.

Trends in adverse events and related health-care facility utilization from cough and cold medication exposures in children.

INTRODUCTION: Initial research following regulatory changes addressing the pediatric safety of cough and cold medications (CCMs) demonstrated decreases in adverse events (AEs). Using a national multi-source surveillance system, we studied subsequent CCM-related AE case rate trends and associated health-care facility (HCF) evaluation in children. METHODS: Data were collected from 2009 to 2016. Case eligibility included: age <12 years; exposure to an over-the-counter product containing ≥1 CCM pharmaceutical ingredient; ≥1 significant AE that occurred in the United States. RESULTS: About 4756 (72.6%) cases were determined at least potentially related to an index ingredient. Accidental unsupervised ingestions (AUIs; 3134; 65.9%) were the most common case type. Nearly half of AE cases involved children 2 to <4 years old (2,159; 45.4%). The AE case rate did not change significantly over time (p = 0.22). The proportion of AE cases resulting in HCF admission increased from 32.4% (207) in 2009 to 43.4% (238) in 2016 (p < 0.01). Exposures to diphenhydramine (1,305; 67.3%) and/or dextromethorphan (591; 30.5%) were involved in the majority of HCF admissions. CONCLUSIONS: The proportion of AE cases resulting in HCF admission increased from 2009 to 2016. Efforts to prevent AUIs such as packaging innovation and engineering controls, particularly for diphenhydramine and dextromethorphan-containing products, should be pursued.

Medication Errors From Over-the-Counter Cough and Cold Medications in Children.

OBJECTIVE: Out of hospital medication-related adverse events (AEs) from cough and cold medications (CCMs) can have significant public health impact. The objective of this study was to characterize pediatric medication error AEs involving over-the-counter (OTC) CCMs to identify preventable factors. METHODS: Multisource national data surveillance system study using an expert panel evaluating CCM AEs related to medication errors. INCLUSION CRITERIA: age <12 years, and at least 1 significant AE from at least 1 index ingredient from a CCM OTC product. RESULTS: From 2009 through 2016, 4756 cases were determined to have a significant AE related to an OTC CCM ingredient and 513 (10.8%) cases were due to a medication error. Nearly half of medication errors involved children 2 to <6 years old (n = 235; 45.8%). Many involved administration by a parent (n = 231; 45.0%) or alternative caregiver (n = 148; 28.8%). In nearly all cases (93.2%), the medication error involved the wrong dose of the medication. Health care facility evaluation occurred in 381 (74.3%) cases. Diphenhydramine and dextromethorphan were responsible for most medication errors and medication errors involving health care facility evaluation. There were no deaths from medication errors. CONCLUSION: In this multiyear surveillance study, medication errors most commonly occurred in children <6 years old who received the wrong volume of a liquid product. Diphenhydramine and dextromethorphan dosing errors were the most common cause of medication errors resulting from CCM use. Continued standardization of measuring devices, concentrations, and units of measure along with consumer education are needed to further decrease medication errors from CCMs.

Antivenom Treatment Is Associated with Fewer Patients using Opioids after Copperhead Envenomation.

INTRODUCTION: Copperhead envenomation causes local tissue destruction, leading people to seek treatment for the pain and swelling. First-line treatment for the pain is opioid medications. There is rising concern that an initial opioid prescription from the emergency department (ED) can lead to long-term addiction. This analysis sought to determine whether use of Fab antivenom (FabAV) for copperhead envenomation affected opioid use. METHODS: We performed a secondary analysis using data from a randomized clinical trial designed to determine the effect of FabAV on limb injury recovery following mild to moderate copperhead envenomation. Opioid use was a defined secondary outcome in the parent trial. Patients were contacted after discharge, and data were obtained regarding medications used for pain and the patients' functional status. This analysis describes the proportion of patients in each treatment group reporting opioid use at each time point. It also assesses the interaction between functional status and use of opioids. RESULTS: We enrolled 74 patients in the parent trial (45 received FabAV, 29 placebo), of whom 72 were included in this secondary analysis. Thirty-five reported use of any opioids after hospital discharge. A smaller proportion of patients treated with FabAV reported opioid use: 40.9% vs 60.7% of those in the placebo group. The proportion of patients using opioids remained smaller in the FabAV group at each follow-up time point. Controlling for confounders and interactions between variables, the model estimated that the odds ratio of using opioids after hospital discharge among those who received placebo was 5.67 times that of those who received FabAV. Patients who reported higher baseline pain, those with moderate as opposed to mild envenomation, and females were more likely to report opioid use at follow-up. Patients with ongoing limitations to functional status had an increased probability of opioid use, with a stronger association over time. Opioid use corresponded with the trial's predefined criteria for full recovery, with only two patients reporting opioid use in the 24 hours prior to achieving full limb recovery and no patients in either group reporting opioid use after full limb recovery. CONCLUSION: In this study population, the proportion of patients using opioids for pain related to envenomation was smaller in the FabAV treatment group at all follow-up time points.

Early administration of Fab antivenom resulted in faster limb recovery in copperhead snake envenomation patients.

BACKGROUND: No previous research has studied whether early snake antivenom administration leads to better clinical outcomes than late antivenom administration in North American pit viper envenomation. METHODS: A secondary analysis of data from a clinical trial of Fab antivenom (FabAV) versus placebo for copperhead snake envenomation was conducted. Patients treated before the median time to FabAV administration were classified as receiving early treatment and those treated after the median time were defined as the late treatment group. A Cox proportional hazards model was used to compare time to full recovery on the Patient-Specific Functional Scale (PSFS) instrument between groups. Secondary analyses compared estimated mean PSFS scores using a generalized linear model and the estimated proportion of patients with full recovery at each time point using logistic regression. To evaluate for confounding, the main analysis was repeated using data from placebo-treated subjects. RESULTS: Forty-five subjects were treated with FabAV at a median of 5.47 h after envenomation. Patients in the early treatment group had a significantly shorter time to full recovery than those treated late (median time: 17 versus 28 days, p = .025). Model-estimated PSFS scores were numerically higher at each time point in the early group. No difference was found between patients treated early versus late with placebo. CONCLUSIONS: In this secondary analysis of trial data, recovery of limb function was faster when Fab antivenom was administered soon after envenomation, as opposed to late administration.