Consistency Between Opioid-Related Mortality Trends Derived From Poison Center and National Vital Statistics System, United States, 2006-2016.

OBJECTIVES: To determine the association between poison center opioid exposure calls and National Vital Statistics System (NVSS) deaths. METHODS: We categorized Centers for Disease Control and Prevention NVSS mortality and the Researched Abuse, Diversion and Addiction-Related Surveillance System poison center program cases from 2006 to 2016 by International Classification of Diseases, Tenth Revision, codes (heroin [T40.1]; natural or semisynthetic opioids [T40.2]; methadone [T40.3]; synthetic opioids, other than methadone [T40.4]). We scaled rates by 100 000 population and calculated Pearson correlation coefficients. Sensitivity analysis excluded polysubstance cases involving either heroin or synthetic opioids as well as natural and semisynthetic opioids. RESULTS: The NVSS mortality and poison center program exposure rates showed similar trends from 2006 to 2012, and diverged after 2012 for all opioids combined, natural and semisynthetic opioids, and synthetic opioids (r = -0.37, -0.12, and 0.30, respectively). Sensitivity analysis with removal of heroin or synthetic opioid polysubstance deaths markedly improved correlations for all opioids combined and natural and semisynthetic opioids (r = 0.87 and 0.36, respectively). CONCLUSIONS: The NVSS mortality and poison center exposure rates showed similar trends from 2006 to 2012 then diverged, with sensitivity analysis suggesting polysubstance cases also involving heroin or illicit fentanyl as the cause. Public Health Implications. The NVSS and poison center program may provide complementary data when trends diverge. Public health interventions must include both licit and illicit opioids for maximal impact.

Frequency of Poison Center Exposures for Pediatric Accidental Unsupervised Ingestions of Acetaminophen after the Introduction of Flow Restrictors.

OBJECTIVE: To assess the temporal association of flow restrictor introduction and the rate of accidental unsupervised ingestions (AUIs) of liquid acetaminophen products. STUDY DESIGN: The National Poison Data System was used to identify AUIs of single ingredient acetaminophen in patients aged <12 years reported between 2007 and 2015. Six regional poison centers obtained additional information using a structured telephone survey. RESULTS: Pediatric AUIs involving acetaminophen averaged 30 000 exposures per year between 2007 and 2012. From 2012 to 2015, after flow restrictor introduction, exposures steadily decreased at a rate of 2400 fewer exposures annually, reaching 21 877 exposures in 2015. Normalized to sales volume, exposures involving liquid acetaminophen products decreased by 40% from 2010 to 2015. Exposures involving products with flow restrictors tended to have a lower estimated ingestion per exposure, fewer exposures exceeding a 150 mg/kg acetaminophen threshold, and were associated with lower rates of hospital admissions when compared with products without restrictors. Caregivers reported improper storage and child confusion of the medicine with treats as common contributing factors to exposures. CONCLUSIONS: The introduction of flow restrictors was associated with a decrease in pediatric AUIs of liquid acetaminophen products. Decreases in the dose ingested and risk of hospital admission per exposure may also have resulted. Efforts to optimize flow restrictors and increase their use with medicines associated with high pediatric overdose risk should be encouraged.

Assessment of Tapentadol API Abuse Liability With the Researched Abuse, Diversion and Addiction-Related Surveillance System.

Tapentadol, a Schedule II opioid with a combination of µ-opioid activity and norepinephrine reuptake inhibition, is used for the management of moderate to severe acute and chronic pain. Its dual mechanism of action is thought to reduce opioid-related side effects that can complicate pain management. Since approval, tapentadol has been tracked across multiple outcomes suggesting abuse liability, and a pattern of relatively low, although not absent, abuse liability has been found. This retrospective cohort study further details the abuse liability of tapentadol as an active pharmaceutical ingredient (API) when immediate-release as well as extended-release formulations were on the market together (fourth quarter of 2011 to second quarter of 2016). Tapentadol (API) was compared with tramadol, hydrocodone, morphine, oxycodone, hydromorphone, and oxymorphone across Poison Center, Drug Diversion, and Treatment Center Programs Combined data streams from the Researched Abuse, Diversion and Addiction-Related Surveillance system. Findings suggest the public health burden related to tapentadol to date is low, but present. Event rates of abuse per population-level denominators were significantly lower than all other opioids examined. However, when adjusted for drug availability, event rates of abuse were lower than most Schedule II opioids studied, but were not the lowest. Disentangling these 2 sets of findings further by examining various opioid formulations, such as extended-release and the role of abuse-deterrent formulations, is warranted. PERSPECTIVE: This article presents the results from an examination of tapentadol API across the Researched Abuse, Diversion and Addiction-Related Surveillance System: a broad and carefully designed postmarketing mosaic. Data to date from Poison Center, Drug Diversion, and Treatment Centers combined suggest a low, but present public health burden related to tapentadol.

Serum Acetaminophen Protein Adduct Concentrations in Pediatric Emergency Department Patients.

OBJECTIVES: Acetaminophen toxicity is a common cause of pediatric liver failure. The diagnosis may be limited by the short window of detection of acetaminophen in serum. Recently acetaminophen protein adducts (APAP-CYS) have been used as a biomarker with a longer duration of detection. The objective of this study was to describe the serum concentrations of APAP-CYS in pediatric patients with and without reported therapeutic acetaminophen exposure. METHODS: A cross-sectional study of children age 1 to <12 years presenting to a pediatric emergency department. Subjects were stratified by recent acetaminophen use and had serum APAP-CYS measured using LC/MS. RESULTS: One hundred patients were enrolled. All of the patients whose caregivers denied acetaminophen exposure had nondetectable APAP-CYS. Fifty-two percent of subjects who were reported to have taken acetaminophen in the preceding 2 weeks had detectable serum APAP-CYS. The APAP-CYS concentrations were positively correlated with higher overall dose and more recent ingestion. CONCLUSIONS: APAP-CYS is detectable in the majority of children taking acetaminophen and not detected in the majority of children who are not exposed to acetaminophen.

Root causes, clinical effects, and outcomes of unintentional exposures to buprenorphine by young children.

OBJECTIVE: To characterize the rates, root causes, and clinical effects of unintentional exposures to buprenorphine sublingual formulations among young children and to determine whether exposure characteristics differ between formulations. STUDY DESIGN: Unintentional exposures to buprenorphine-containing products among children 28 days to less than 6 years old were collected from the Researched Abuse, Diversion, and Addiction-Related Surveillance System Poison Center Program and Reckitt Benckiser Pharmaceuticals' pharmacovigilance system from October 2009-March 2012. After adjustment for drug availability, negative binomial regression was used to estimate average exposure rates. Root cause assessment was conducted, and an expert clinician panel adjudicated causality and severity of moderate to severe adverse events (AEs). RESULTS: A total of 2380 cases were reviewed, including 4 deaths. Exposures to buprenorphine-naloxone combination film were significantly less frequent than exposures to buprenorphine tablets (rate ratio 3.5 [95% CI, 2.7-4.5]) and buprenorphine-naloxone combination tablets (rate ratio 8.8 [7.2-10.6]). The most commonly identified root causes were medication stored in sight, accessed from a bag or purse, and not stored in the original packaging. Among 536 panel review cases, the most common AEs reported for all formulations were lethargy, respiratory depression, miosis, and vomiting. The highest level AE severity did not differ significantly by formulation. CONCLUSIONS: Unintentional exposure to buprenorphine can cause central nervous system depression, respiratory depression, and death in young children. Exposure rates to film formulations are significantly less than to tablet formulations. Package and storage deficiencies contribute to unintentional exposures in young children.