Trends in rates of acetaminophen-related adverse events in the United States.

PURPOSE: The goal of this study is to summarize trends in rates of adverse events attributable to acetaminophen use, including hepatotoxicity and mortality. METHODS: A comprehensive analysis of data from three national surveillance systems estimated rates of acetaminophen-related events identified in different settings, including calls to poison centers (2008-2012), emergency department visits (2004-2012), and inpatient hospitalizations (1998-2011). Rates of acetaminophen-related events were calculated per setting, census population, and distributed drug units. RESULTS: Rates of poison center calls with acetaminophen-related exposures decreased from 49.5/1000 calls in 2009 to 43.5/1000 calls in 2012. Rates of emergency department visits for unintentional acetaminophen-related adverse events decreased from 58.0/1000 emergency department visits for adverse drug events in 2009 to 50.2/1000 emergency department visits in 2012. Rates of hospital inpatient discharges with acetaminophen-related poisoning decreased from 119.8/100 000 hospitalizations in 2009 to 108.6/100 000 hospitalizations in 2011. After 2009, population rates of acetaminophen-related events per 1 million census population decreased for poison center calls and hospitalizations, while emergency department visit rates remained stable. However, when accounting for drug sales, the rate of acetaminophen-related events (per 1 million distributed drug units) increased after 2009. Prior to 2009, the rates of acetaminophen-related hospitalizations had been slowly increasing (p-trend = 0.001). CONCLUSIONS: Acetaminophen-related adverse events continue to be a public health burden. Future studies with additional time points are necessary to confirm trends and determine whether recent risk mitigation efforts had a beneficial impact on acetaminophen-related adverse events. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

Eosinophilic pneumonia in patients treated with daptomycin: review of the literature and US FDA adverse event reporting system reports.

BACKGROUND: Eosinophilic pneumonia (EP) has been noted in association with daptomycin use. The product labelling was recently updated to include EP in the Warnings and Precautions and Post-Marketing Experience sections. OBJECTIVE: The objective of this study was to analyse adverse event (AE) reports submitted to the US FDA as well as published cases to characterize the clinical features and course of EP in daptomycin-treated patients. METHODS: We searched for EP cases associated with daptomycin administration in the FDA Adverse Event Reporting System (AERS) submitted from 2004 to 2010, and the published literature. Cases were defined as definite, probable, possible and unlikely in terms of the diagnosis of EP and the potential association with daptomycin exposure. Definite cases had concurrent exposure to daptomycin, fever, dyspnoea with increased oxygen requirement or required mechanical ventilation, new infiltrates on chest imaging, bronchoalveolar lavage with >25% eosinophils and clinical improvement following daptomycin withdrawal. Additionally, we assessed inpatient daptomycin utilization. RESULTS: We identified 7 definite, 13 probable, 38 possible cases of daptomycin-induced EP, and 23 unlikely cases. The seven definite EP cases had resolution after daptomycin was stopped, including two with EP recurrence following daptomycin rechallenge. Regarding the definite cases: (i) ages ranged from 60 to 87 years; (ii) dosing ranged from 4.4 to 8.0 mg/kg/day; and (iii) EP developed 10 days to 4 weeks after starting daptomycin. There was a gradual increase in the number of patients with an inpatient hospital discharge billing for daptomycin from the year 2004 to 2010. CONCLUSIONS: We report 7 definite, 13 probable and 38 possible EP cases associated with daptomycin administration. As AERS is based on voluntary reporting, the incidence of EP cannot be assessed. Healthcare providers should have heightened awareness of this serious AE associated with daptomycin use.