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.

Candidate metrics for evaluating the impact of prescriber education on the safe use of extended-release/long-acting (ER/LA) opioid analgesics.

OBJECTIVE: The objective of this study was to develop metrics to assess opioid prescribing behavior as part of the evaluation of the Extended-Release/Long-Acting (ER/LA) Opioid Analgesic Risk Evaluation and Mitigation Strategies (REMS). DESIGN: Candidate metrics were selected using published guidelines, examined using sensitivity analyses, and applied to cross-sectional rolling cohorts of Medicare patients prescribed with extended-release oxycodone (ERO) between July 2, 2006 and July 1, 2011. Potential metrics included prescribing opioid-tolerant-only ER/LA opioid analgesics to non-opioid-tolerant patients, prescribing early fills to patients, and ordering drug screens. RESULTS: Proposed definitions for opioid tolerance were seven continuous days of opioid usage of at least 30 mg oxycodone equivalents, within the 7 days (primary) or 30 days (secondary) prior to first opioid-tolerant-only ERO prescription. Forty-four percent of opioid-tolerant-only ERO episodes met the primary opioid tolerance definition; 56% met the secondary definition. Fills were deemed "early" if a prescription was filled before 70% (primary) or 50% (secondary) of the prior prescription's days' supply was to be consumed. Five percent (primary) and 2% (secondary) of episodes had more than or equal to two early fills during treatment. At least one drug screen was billed in 14% of episodes. Stratified analyses indicated that older patients were less likely to be opioid tolerant at the time of the first opioid-tolerant-only ERO prescription. CONCLUSIONS: Investigators propose three metrics to monitor changes in prescribing behaviors for opioid analgesics that might be used to evaluate the ER/LA Opioid Analgesics REMS. Low frequencies of patients, particularly those >85 years, were likely to be opioid tolerant prior to receiving prescriptions for opioid-tolerant-only ERO.

Characterization of acetaminophen overdose-related emergency department visits and hospitalizations in the United States.

PURPOSE: To estimate the number of acetaminophen overdose-related emergency department (ED) visits and hospitalizations in the United States, characterize these by intentionality, age, and gender, and compare the strengths and limitations of the utilized databases. METHODS: We used data from the National Hospital Ambulatory Medical Care Survey (NHAMCS) and the National Electronic Injury Surveillance System (NEISS) to estimate the number of relevant ED visits in the United States between 2000 and 2007, and the National Hospital Discharge Survey (NHDS) to estimate the number of relevant hospitalizations in the United States between 1991 and 2006. National estimates and their standard errors were calculated using information provided in each database. We used the standard United States population in 2000 to calculate age-adjusted rates. RESULTS: We estimate an annual average of 44,348 (NHAMCS, 2000-2007) or 78,414 (NEISS, 2006-2007) acetaminophen overdose-related ED visits and 33,520 (NHDS, 2000-2006) hospitalizations. For 2000-2006 we calculated an age-adjusted rate of 13.9 acetaminophen overdose-related hospitalizations per 100,000 US population, with the highest rate (15.7) occurring from 2005 to 2006. Between 1991 and 2006, there was no decrease noted in hospitalizations for intentional or unintentional overdoses. The majority of overdoses reported in NEISS (69.8%) and NHDS (74.2%) were classified as intentional (suicides or suicidal gestures), whereas in NHAMCS, intentionality was evenly distributed. CONCLUSIONS: Our results suggest that acetaminophen overdose, both intentional and unintentional, remains a significant public health concern. With an understanding of their methodological characteristics and limitations, these national databases can be useful tools to characterize acetaminophen overdose-related ED visits and hospitalizations.

Antidepressant medication use and risk of persistent pulmonary hypertension of the newborn.

PURPOSE: To determine the prevalence of persistent pulmonary hypertension of the newborn (PPHN) among infants whose mothers were exposed to antidepressants in the third trimester of pregnancy compared to the prevalence among infants whose mothers were not exposed to antidepressants in the third trimester. METHODS: A retrospective study was conducted using the automated databases of four health plans participating in the HMO Research Network Center for Education and Research on Therapeutics. Women who delivered an infant in a hospital from 1 January 1996 through 31 December 2000 were identified. The administrative databases were used to identify full-term infants whose mothers received an antidepressant during the third trimester of pregnancy and unexposed infants whose mothers did not receive an antidepressant during the third trimester. Hospitalization data were used to identify diagnoses or procedure codes potentially indicative of PPHN. RESULTS: Among 1104 infants exposed to antidepressants in the third trimester and a matched sample of 1104 unexposed infants, five infants were classified by the expert reviewers as having PPHN. Among those infants whose mothers were exposed to selective serotonin reuptake inhibitors (SSRIs) in the third trimester, the prevalence of PPHN was 2.14 per 1000 (95% confidence interval (CI) 0.26, 7.74), while the prevalence among infants whose mothers were not exposed was 2.72 per 1000 (95%CI 0.56, 7.93). CONCLUSIONS: We did not find an association between SSRI use in late pregnancy and PPHN. Limitations of the present study, including the small number of confirmed cases, suggest further research in this area may be warranted.

Drug-risk communication to pharmacists: assessing the impact of risk-minimization strategies on the practice of pharmacy.

OBJECTIVES: To gain insight on the knowledge, opinions, barriers, and practices of pharmacists regarding drug risk-minimization tools. DESIGN: Descriptive, nonexperimental, cross-sectional survey. SETTING: 20 states in the United States, fall 2004. PARTICIPANTS: 2,052 randomly selected licensed pharmacists employed in a position requiring an active pharmacist license at the time of the survey and who responded to the survey. INTERVENTION: Participants completed a four-page survey regarding their experience with different types of risk-minimization tools. MAIN OUTCOME MEASURE: Univariate distributions for each question were analyzed. RESULTS: 50% of survey recipients responded to the mailing; 88% of respondents had an active pharmacist license. Of respondents, 18% reported never having received a Dear Healthcare Professional letter and 29% stated that they were not familiar with Medication Guides. Patient package inserts were thought to be somewhat effective by 53% of respondents. Of pharmacists who dispensed a drug with programs for special stickers to be affixed on prescriptions to indicate that the labeled risk had been addressed by the prescriber, 41% reported receiving a prescription without a sticker; 45% dispensed the prescription when stickers were missing. Sixty percent of pharmacists stated that risk-minimization programs have a negative impact on the daily practice of pharmacy; nevertheless, many acknowledged that it was a necessary duty. CONCLUSION: Pharmacists might benefit from additional training on risk-minimization strategies. The successful implementation and impact of risk-minimization programs on the practice of pharmacy should be carefully considered by drug manufacturers and regulators.

Use of antidepressant medications during pregnancy: a multisite study.

OBJECTIVE: This study was undertaken to provide information on the prevalence of use of antidepressant drugs among pregnant women in the United States. STUDY DESIGN: A retrospective study was conducted using the automated databases of 7 health plans. Women who delivered an infant in a hospital were identified. Antidepressant drug use was evaluated assuming a gestational duration of 270 days. RESULTS: Among the 118,935 deliveries occurring from 2001-2005, 6.6% of women were dispensed an antidepressant during pregnancy. Antidepressant drug use increased from 2.0% in 1996 to 7.6% of deliveries in 2004 and 2005. Selective serotonin reuptake inhibitor use increased from 1.5% in 1996 to 6.4% in 2004 and 6.2% in 2005. CONCLUSION: Our finding that nearly 8% of pregnant women were prescribed antidepressants drugs during the years 2004 and 2005 highlights the importance of understanding the effects of these medications on the developing fetus and on the pregnant woman.

Increasing use of antidepressants in pregnancy.

OBJECTIVE: The purpose of this study was to quantify the rate of exposures to antidepressants during pregnancy in a large cohort of women. STUDY DESIGN: This was a retrospective cohort study of 105,335 pregnancies among women enrolled in Tennessee Medicaid from 1999-2003. Pregnancies were classified according to antidepressant exposures during pregnancy using previously validated computerized pharmacy records linked with birth certificates. RESULTS: During the study period, 8.7% of women giving birth had exposure to any antidepressant; 6.2% had exposure to a selective serotonin reuptake inhibitor. Maternal age > 25 years (P < .0001), white race (P < .0001), and education > 12 years (P = .008) were significant predictors of antidepressant exposure. The proportion of pregnancies with antidepressant use increased from 5.7% of pregnancies in 1999 to 13.4% of pregnancies in 2003 (p < .0001). The increase was mostly accounted for by increases in selective serotonin reuptake inhibitor exposures. CONCLUSION: There is an urgent need for further studies that better quantify the fetal consequences of exposure to antidepressants.

What is prescription labeling communicating to doctors about hepatotoxic drugs? A study of FDA approved product labeling.

PURPOSE: The objective of this study was to evaluate the informativeness and consistency of product labeling of hepatotoxic drugs marketed in the United States. METHODS: We searched the Physicians' Desk Reference-2000 for prescription drugs with hepatic failure and/or hepatic necrosis listed in the labeling. We used a six-item checklist to evaluate the 'informativeness' and consistency of the labeling content. An informativeness score equaled the proportion of checklist items present in each drug's labeling. RESULTS: Ninety-five prescription drugs were included in the study. Eleven (12%) of the drugs had information related to hepatic failure in a Black Boxed Warning, 52 (54%) in the Warnings section and 32 (34%) in the Adverse Reactions section of the label. The mean informativeness score was 35%; the score was significantly higher, 61%, when the risk was perceived to be high. The informativeness of labeling was not affected by the time of the labeling, but differed across the Center for Drug Evaluation and Research (CDER) Review Division responsible for the labeling. CONCLUSIONS: The information provided in labeling is variable and affected by many factors, including the perceived level of risk and review division strategy. Product labeling may benefit from current FDA initiatives to improve the consistency of risk-related labeling.

A study of compliance with FDA recommendations for pemoline (Cylert).

OBJECTIVE: To assess compliance with product labeling recommendations to use pemoline as second-line therapy for attention-deficit/hyperactivity disorder (ADHD) and to obtain baseline and biweekly liver enzyme tests. METHOD: Retrospective cohort study using administrative claims data to identify first-line therapies and liver enzyme tests among pemoline users between January 1, 1998, and March 31, 2000. Prescriptions for first-line therapy were searched for 90 days prior to the first pemoline claim. Liver enzyme testing (baseline and follow-up) was compared between two groups (the prerecommendation cohort October 1,1998, to March 31, 1999, and the postrecommendation cohort October 1,1999, to March 31,2000). RESULTS: 1,308 patients received at least one pemoline prescription during the study period; 76% of patients < or = 20 years were male. ADHD was the claims-identified indication for 688 patients (52%). Despite the labeling recommendation for use as second-line therapy, only 237 ADHD patients (34%) received a first-line therapy prior to pemoline. Only 12% and 11% of the pre- and post-cohort patients, respectively, received baseline liver enzyme tests; 9% in the pre- and 12% in the post-cohort received at least one liver enzyme follow-up test. CONCLUSIONS: Compliance with product labeling was low for both recommendations. Understanding the reasons for this finding could help improve risk management strategies.