Spontaneous Adverse Event Reports Research Articles

Four Decade Cumulative Review of Thrombo-Embolic Events Reported with the Use of Activated Prothrombin Complex Concentrate in Congenital Haemophilia

Introduction and Objectives: The use of bypassing agents have contributed to a better management of bleeding (prevention and treatment) of persons with haemophilia (PWH) and inhibitors. One of these, an activated prothrombin complex concentrate (APCC - FEIBA - FVIII inhibitor bypassing activity, Shire) became commercially available 40 years ago in 1975. While bypassing therapy has been proven effective, it introduced a potentially increased risk of treatment-associated thrombo-embolic events (TEEs). The small size of clinical trials and post-authorization surveillance studies in PWH with inhibitors limits the capability to ascertain risk factors for APCC-associated TEEs. The present review provides an overview of clinical details of all spontaneous and literature cases TEEs reported with the use of APCC in congenital haemophilia, documented in the Company's global safety database.Materials and Methods: The global safety database was reviewed for all spontaneous and literature adverse events reports of APCC received from 1975 through July 2016, addressing patient demographics, dosing regimens, confounding and risk factors deemed relevant for the development of TEEs in temporal association with APCC treatment.Results: More than 7 billion units of APCC (more than 2million infusions) were distributed during the review period. Overall 108 TEE have been reported in patients with different indications (congenital haemophilia, acquired haemophilia, anticoagulation reversal, etc.). Of these, 85 reports including one or more thromboembolic events were received for PWH (thereof 60 spontaneous reports), aged 0-73 years (mean 32, median 22). Of the 85 TEEs, 13 were reported as deep vein thrombosis and/or pulmonary embolism (median age: 11 years, min-max 3-22), 32 as myocardial infarction or stroke (median age: 41 years; min-max 8-73), 18 as disseminated intravascular coagulation (median age: 49; min-max: 0-71) and 22 as other events (median age: 30 years; min-max: 3-57). Of the 85 TEEs, 31 TEEs were reported with rFVIIa as a concomitant medication (7 DVT/PE, 9 MI/stroke, 9 DIC, 6 others).Conclusion: The reporting rate of TEEs associated with APCC remains comparable with data published earlier and confirms its long-time overall safety profile. Moreover, the majority of the TEEs occurred in the presence of additional/confounding risk factors such as underlying disease and concomitant medications. The review of clinical details of all TEEs reported in temporal association with the use of APCC is a valuable resource for the understanding and perhaps the prevention. DisclosuresCrea:Shire: Employment, Equity Ownership. Novack:Shire: Employment, Equity Ownership. Reininger:Shire: Employment, Equity Ownership. Kennedy:Shire: Employment, Equity Ownership. Raff:Shire: Employment, Equity Ownership. Gringeri:Shire: Employment, Equity Ownership. Bajwa:Shire: Employment, Equity Ownership.

Spontaneous adverse event reports associated with zolpidem

Spontaneous adverse event reports associated with zolpidem

Association between Selective Beta-adrenergic Drugs and Blood Pressure Elevation: Data Mining of the Japanese Adverse Drug Event Report (JADER) Database.

Selective beta-adrenergic drugs are used clinically to treat various diseases. Because of imperfect receptor selectivity, beta-adrenergic drugs cause some adverse drug events by stimulating other adrenergic receptors. To examine the association between selective beta-adrenergic drugs and blood pressure elevation, we reviewed the Japanese Adverse Drug Event Reports (JADERs) submitted to the Japan Pharmaceuticals and Medical Devices Agency. We used the Medical Dictionary for Regulatory Activities (MedDRA) Preferred Terms extracted from Standardized MedDRA queries for hypertension to identify events related to blood pressure elevation. Spontaneous adverse event reports from April 2004 through May 2015 in JADERs, a data mining algorithm, and the reporting odds ratio (ROR) were used for quantitative signal detection, and assessed by the case/non-case method. Safety signals are considered significant if the ROR estimates and lower bound of the 95% confidence interval (CI) exceed 1. A total of 2021 reports were included in this study. Among the nine drugs examined, significant signals were found, based on the 95%CI for salbutamol (ROR: 9.94, 95%CI: 3.09-31.93) and mirabegron (ROR: 7.52, 95%CI: 4.89-11.55). The results of this study indicate that some selective beta-adrenergic drugs are associated with blood pressure elevation. Considering the frequency of their indications, attention should be paid to their use in elderly patients to avoid adverse events.

Bayesian model selection in logistic regression for the detection of adverse drug reactions.

Spontaneous adverse event reports have a high potential for detecting adverse drug reactions. However, due to their dimension, the analysis of such databases requires statistical methods. In this context, disproportionality measures can be used. Their main idea is to project the data onto contingency tables in order to measure the strength of associations between drugs and adverse events. However, due to the data projection, these methods are sensitive to the problem of coprescriptions and masking effects. Recently, logistic regressions have been used with a Lasso type penalty to perform the detection of associations between drugs and adverse events. On different examples, this approach limits the drawbacks of the disproportionality methods, but the choice of the penalty value is open to criticism while it strongly influences the results. In this paper, we propose to use a logistic regression whose sparsity is viewed as a model selection challenge. Since the model space is huge, a Metropolis-Hastings algorithm carries out the model selection by maximizing the BIC criterion. Thus, we avoid the calibration of penalty or threshold. During our application on the French pharmacovigilance database, the proposed method is compared to well-established approaches on a reference dataset, and obtains better rates of positive and negative controls. However, many signals (i.e., specific drug-event associations) are not detected by the proposed method. So, we conclude that this method should be used in parallel to existing measures in pharmacovigilance. Code implementing the proposed method is available at the following url: https://github.com/masedki/MHTrajectoryR.

Data mining spontaneous adverse drug event reports for safety signals in Singapore – a comparison of three different disproportionality measures

ABSTRACTObjectives: Quantitative data mining methods can be used to identify potential signals of unexpected relationships between drug and adverse event (AE). This study aims to compare and explore the use of three data mining methods in our small spontaneous AE database.Methods: We consider reporting odds ratio (ROR), Bayesian Confidence Propagation Neural Network (BCPNN) and Gamma Poisson Shrinker (GPS) assuming two different sets of criteria: (1) ROR–1.96SE>1, IC–1.96SD>0, EB05>1 (2) ROR–1.96SE>2, IC–1.96SD>1, EB05 >2. Count of drug-AE pairs ≥3 was considered for ROR and GPS.Results: The Health Sciences Authority, Singapore received 151,180 AE reports between 1993 and 2013. ROR, BCPNN and GPS identified 2,835, 2,311 and 2,374 significant drug-AE pairs using Criterion 1, and 1,899, 1,101 and 1,358 respectively using Criterion 2. The performance of the three methods with respect to specificity, positive predictive value and negative predictive value were similar, although ROR yielded a higher sensitivity and larger area under the receiver operating characteristic curve. ROR and GPS picked up some potential signals which BCPNN missed.Conclusions: The defined threshold used for ROR (Criterion 1) is a useful screening tool for our small database. It may be used in conjunction with GPS to avoid missed signals.

Social Media Listening for Routine Post-Marketing Safety Surveillance.

Post-marketing safety surveillance primarily relies on data from spontaneous adverse event reports, medical literature, and observational databases. Limitations of these data sources include potential under-reporting, lack of geographic diversity, and time lag between event occurrence and discovery. There is growing interest in exploring the use of social media ('social listening') to supplement established approaches for pharmacovigilance. Although social listening is commonly used for commercial purposes, there are only anecdotal reports of its use in pharmacovigilance. Health information posted online by patients is often publicly available, representing an untapped source of post-marketing safety data that could supplement data from existing sources. The objective of this paper is to describe one methodology that could help unlock the potential of social media for safety surveillance. A third-party vendor acquired 24months of publicly available Facebook and Twitter data, then processed the data by standardizing drug names and vernacular symptoms, removing duplicates and noise, masking personally identifiable information, and adding supplemental data to facilitate the review process. The resulting dataset was analyzed for safety and benefit information. In Twitter, a total of 6,441,679 Medical Dictionary for Regulatory Activities (MedDRA(®)) Preferred Terms (PTs) representing 702 individual PTs were discussed in the same post as a drug compared with 15,650,108 total PTs representing 946 individual PTs in Facebook. Further analysis revealed that 26% of posts also contained benefit information. Social media listening is an important tool to augment post-marketing safety surveillance. Much work remains to determine best practices for using this rapidly evolving data source.

Can Natural Language Processing Improve the Efficiency of Vaccine Adverse Event Report Review?

Individual case review of spontaneous adverse event (AE) reports remains a cornerstone of medical product safety surveillance for industry and regulators. Previously we developed the Vaccine Adverse Event Text Miner (VaeTM) to offer automated information extraction and potentially accelerate the evaluation of large volumes of unstructured data and facilitate signal detection. To assess how the information extraction performed by VaeTM impacts the accuracy of a medical expert's review of the vaccine adverse event report. The "outcome of interest" (diagnosis, cause of death, second level diagnosis), "onset time," and "alternative explanations" (drug, medical and family history) for the adverse event were extracted from 1000 reports from the Vaccine Adverse Event Reporting System (VAERS) using the VaeTM system. We compared the human interpretation, by medical experts, of the VaeTM extracted data with their interpretation of the traditional full text reports for these three variables. Two experienced clinicians alternately reviewed text miner output and full text. A third clinician scored the match rate using a predefined algorithm; the proportion of matches and 95% confidence intervals (CI) were calculated. Review time per report was analyzed. Proportion of matches between the interpretation of the VaeTM extracted data, compared to the interpretation of the full text: 93% for outcome of interest (95% CI: 91-94%) and 78% for alternative explanation (95% CI: 75-81%). Extracted data on the time to onset was used in 14% of cases and was a match in 54% (95% CI: 46-63%) of those cases. When supported by structured time data from reports, the match for time to onset was 79% (95% CI: 76-81%). The extracted text averaged 136 (74%) fewer words, resulting in a mean reduction in review time of 50 (58%) seconds per report. Despite a 74% reduction in words, the clinical conclusion from VaeTM extracted data agreed with the full text in 93% and 78% of reports for the outcome of interest and alternative explanation, respectively. The limited amount of extracted time interval data indicates the need for further development of this feature. VaeTM may improve review efficiency, but further study is needed to determine if this level of agreement is sufficient for routine use.

有害事象自発報告データベースに基づく経口血糖降下薬による低血糖症発現リスクに関する研究

有害事象自発報告データベースに基づく経口血糖降下薬による低血糖症発現リスクに関する研究

Analysis of licorice-induced pseudoaldosteronism in the Japanese Adverse Drug Event Report database

Aim We analyzed the association of age, sex, and dosage with licorice-associated pseudoaldosteronism using spontaneous adverse event reports. Methods Pseudoaldosteronism incidence data from 2004 to 2013 were obtained from the Japanese Adverse Drug Event Report (JADER) database. These reports were analyzed using a reporting odds ratio (ROR). Medical Dictionary for Regulatory Activities-preferred terms were used to identify pseudoaldosteronism. Results Pseudoaldosteronism was reported frequently in female patients aged >50 years. ROR of pseudoaldosteronism were calculated and stratified by licorice dosage. ROR (95%CI) for doses <2.5, 2.5–4.9, and ≥5.0 g were 20.9 (15.1–28.8), 26.1 (15.1–45.0), and 147.3 (150.3–206.0), respectively. Conclusion Despite the limitations of spontaneous reporting, licorice dosage may be associated with pseudoaldosteronism. Considering the causality restraint of the current analysis, further epidemiological studies are recommended.

Spontaneous Adverse drug event reports to the Adverse Drug Event Manager (ADEM)

Spontaneous Adverse drug event reports to the Adverse Drug Event Manager (ADEM)

Effect of database profile variation on drug safety assessment: an analysis of spontaneous adverse event reports of Japanese cases.

BackgroundThe use of a statistical approach to analyze cumulative adverse event (AE) reports has been encouraged by regulatory authorities. However, data variations affect statistical analyses (eg, signal detection). Further, differences in regulations, social issues, and health care systems can cause variations in AE data. The present study examined similarities and differences between two publicly available databases, ie, the Japanese Adverse Drug Event Report (JADER) database and the US Food and Drug Administration Adverse Event Reporting System (FAERS), and how they affect signal detection.MethodsTwo AE data sources from 2010 were examined, ie, JADER cases (JP) and Japanese cases extracted from the FAERS (FAERS-JP). Three methods for signals of disproportionate reporting, ie, the reporting odds ratio, Bayesian confidence propagation neural network, and Gamma Poisson Shrinker (GPS), were used on drug-event combinations for three substances frequently recorded in both systems.ResultsThe two databases showed similar elements of AE reports, but no option was provided for a shareable case identifier. The average number of AEs per case was 1.6±1.3 (maximum 37) in the JP and 3.3±3.5 (maximum 62) in the FAERS-JP. Between 5% and 57% of all AEs were signaled by three quantitative methods for etanercept, infliximab, and paroxetine. Signals identified by GPS for the JP and FAERS-JP, as referenced by Japanese labeling, showed higher positive sensitivity than was expected.ConclusionThe FAERS-JP was different from the JADER. Signals derived from both datasets identified different results, but shared certain signals. Discrepancies in type of AEs, drugs reported, and average number of AEs per case were potential contributing factors. This study will help those concerned with pharmacovigilance better understand the use and pitfalls of using spontaneous AE data.

PCV25 - Evaluation Of Bleeding Outcomes Linked To New Oral Anticoagulants: Review Of The Fda Adverse Event Reporting System (Faers)

Clinical trials comparing rivaroxaban or dabigatran to warfarin show similar results for major and non-major clinically relevant bleeding. Post-marketing data regarding bleeding rates for these new oral anticoagulants (NOACs) is lacking. Our goal was to evaluate bleeding related outcomes with NOACs using a disproportionality analysis of spontaneous adverse event reports. We evaluated the FAERS database from 10/2011 – 12/2012 to compare frequency of events in reports of rivaroxaban, dabigatran, and warfarin related to fatal and non-fatal bleeding. Reports were included if the anticoagulant was the primary suspected agent for the event. Reporting odds ratio (ROR) and proportional reporting ratio (PRR) were calculated to estimate risk for each anticoagulant. Of 22,244 eligible adverse drug reports for the anticoagulants, 7661 (34%) bleeding reports were submitted, with 1868 (24%) deaths, 5028 (66%) hospitalizations and 1040 (14%) life-threatening events. Dabigatran was the most commonly reported anticoagulant exposure among bleeding cases (n=5203, 68%). Of the bleeding cases associated with dabigatran, death was reported in 29%, hospitalization in 67%, and life-threatening events in 15% of cases. The odds of exposure for fatal bleeding was significantly higher with dabigatran (ROR 2.28, 95% confidence interval [CI] 2.02-2.56) and significantly lower with rivaroxaban (ROR 0.75, CI = 0.69-0.8) and warfarin (ROR 0.53, CI = 0.44-0.63). PRR indicated significantly increased risk of non-fatal bleeding with dabigatran (PRR = 2.12, CI = 1.99-2.24) and warfarin (PRR = 1.27, CI = 1.17-1.38) with a significant decrease associated with rivaroxaban (PRR 0.8, CI = 0.75-0.86). Among the NOACs, patients having fatal and non-fatal bleeding were found to have higher odds of dabigatran exposure and significantly lower odds of rivaroxaban exposure. Though FAERS is subject to significant bias, the results suggest dabigatran-related bleeding is higher in clinical practice and rivaroxaban may be a safer alternative.

Farmacovigilância em Portugal: Atividade da Unidade Regional do Centro

The aim of this study was to characterize the spontaneous reports of adverse events that were received by the Central Portugal Regional Pharmacovigilance Unit. Spontaneous reports received between 01/2001 and 12/2013 were considered. The annual reporting ratios were estimated. The cases were characterized according to their seriousness, previous description, causality assessment, origin and professional group of the reporter, type of adverse event and pharmacotherapeutic groups of the suspected drugs most frequently reported. The Pharmacovigilance Unit received 2408 reports that contained 5749 adverse events. In 2013, the reporting rate was estimated at 171 reports per million inhabitants. Fifty-five percent of the reports were assessed as serious. Ninety percent of the cases were assessed as being at least possibly related with the suspected drug. The suspected drugs most frequently reported were anti-infectives for systemic use (n = 809, 33%). The most frequently reported adverse events were "Skin and subcutaneous tissue disorders" (n = 1139, 20%). There were 154 (6.4%) reports resulting in life-threatening situations and/or death, and 88 (3.6%) containing at least one adverse event assessed as serious, unknown and certain or probable. The present results are in line with those found in other studies, namely the seriousness and type of the adverse events and the pharmacotherapeutic groups of the most frequently reported suspected drugs. In the last years, the Central Portugal Regional Pharmacovigilance Unit has registered a growth in the reporting rate in general, as well as an increase in the reporting of unknown and serious adverse drug reactions.

Hyperglycemic adverse events following antipsychotic drug administration in spontaneous adverse event reports.

BackgroundAntipsychotics are potent dopamine antagonists used to treat schizophrenia and bipolar disorder. The aim of this study was to evaluate the relationship between antipsychotic drugs and adverse hyperglycemic events using the FDA Adverse Event Reporting System (FAERS) database. In particular, we focused on adverse hyperglycemic events associated with atypical antipsychotic use, which are major concerns.FindingsWe analyzed reports of adverse hyperglycemic events associated with 26 antipsychotic drugs in the FAERS database from January 2004 to March 2013. The Standardized Medical Dictionary for Regulatory Activities Queries (SMQ) preferred terms (PTs) was used to identify adverse hyperglycemic events. The number of adverse hyperglycemic reports for the top eight antipsychotic drugs, quetiapine, olanzapine, risperidone, aripiprazole, haloperidol, clozapine, prochlorperazine, and chlorpromazine was 12,471 (28.9%), 8,423 (37.9%), 5,968 (27.0%), 4,045 (23.7%), 3,445 (31.5%), 2,614 (14.3%), 1,800 (19.8%), and 1,003 (35.7%), respectively. The reporting ratio increased with co-administration of multiple antipsychotic drugs. For example, adverse hyperglycemic events represented 21.6% of reports for quetiapine monotherapy, 39.9% for two-drug polypharmacy, and 66.3% for three-drug polypharmacy.ConclusionAntipsychotic drug polypharmacy may influence signal strength, and may be associated with hyperglycemia. After considering the causality restraints of the current analysis, further robust epidemiological studies are recommended.

Intussusception risk after RotaTeq vaccination: Evaluation from worldwide spontaneous reporting data using a self-controlled case series approach

The increased risk of intussusception after vaccination with the rhesus-human reassortant rotavirus vaccine Rotashield led to its withdrawal in 2005. We assess the risk of intussusception following the pentavalent rotavirus vaccine (RV5) on the basis of worldwide reports to the manufacturer up to May 2014, using a self-controlled case series. The method had to be modified to account for the under-reporting, a specific feature of pharmacovigilance spontaneous reports. The risk of intussusception occurring in either of the 0- to 2-day, 3- to 7-day or 8- to 14-day risk periods, was compared to the risk in the 15- to 30-day period. A total of 502 cases occurring 0–30 days after a vaccine dose were studied, including 188 cases after the first dose, 190 cases after the second dose, and 124 cases after the third dose. The incidence risk ratio relative to the control period was highest for the 3- to 7-day period and equal to 3.45 (95% CI 1.84–6.55), 1.63 (0.86–3.13) and 1.73 (0.86–3.51) after the first, second and third dose, respectively. Rotavirus vaccination with RV5 increases the risk of intussusception 3–7 days following vaccination, mainly after the first dose and marginally after the second and third doses. The risk is small and restricted to a short time window. It does not outweigh the benefit of the vaccination, but parents of vaccinated infants should be informed in order to react appropriately to the first symptoms. With appropriate assumptions about the reporting rate, spontaneous reports of adverse events after vaccination can be studied to evaluate vaccine safety.

Analysis of Neuropsychiatric Adverse Events in Patients Treated with Oseltamivir in Spontaneous Adverse Event Reports.

There have been concerns that oseltamivir causes neuropsychiatric adverse events (NPAEs). We analyzed the association of age and gender with NPAEs in patients treated with oseltamivir using a logistic regression model. NPAE data were obtained from the U.S. Food and Drug Administration Adverse Event Reporting System (2004 to 2013). The lower limit of the reporting odds ratio (ROR) 95% confidence interval (CI) of "abnormal behavior" in Japan, Singapore, and Taiwan was ≥1. The effects of the interaction terms for oseltamivir in male patients aged 10-19 years were statistically significant. The adjusted ROR of "abnormal behavior" was 96.4 (95% CI, 77.5-119.9) in male patients aged 10-19 years treated with osletamivir. In female patients, the results of the likelihood ratio test for "abnormal behavior" were not statistically significant. The adjusted NPAE RORs were increased in male and female patients under the age of 20 years. Oseltamivir use could be associated with "abnormal behavior" in males aged 10-19 years. After considering the causality restraints of the current analysis, further epidemiological studies are recommended.

Using data mining of spontaneous adverse event reports and multivariate statistical methods for assessing abuse potential

sample of out-of-treatment (n=10) and in-treatment participants (n=14). Results: The user systemnorm supported trying newdrugs, and both drugs were confirmed to be available in the environment. For the innovation-decision process, knowledge was greater for SCann than SCath as SCath was viewed as causing harm and users were unsure how to ingest it. In contrast SCann was compatible with known drug (i.e., marijuana) and used similarly. Both SCann and SCath were viewed as accessible and inexpensive (i.e., high trialability). The persuasion stage also favored SCann as almost all the users knew someone who had used SCann but few knew anyone who had used SCath. These differences lead to greater implementation of SCann than SCath as evidenced by total admissions, substance abuse treatment providers’ survey, and users’ experiences. However, after SCann and SCathwere removed from shelves due to communitymobilization, health alert, and Scheduling, there was disenchantment discontinuity in the confirmation stage. Few users expressed ongoing demand for synthetic compounds (either SCann or SCath) if theywere not easily available and legal. All users expressed preference for what they called “real” drugs, indicating SCann and SCath had no relative advantage over other drugs of abuse. Conclusions: This qualitative study showed SCann and SCath experienced different and declining demand in this region. Diffusion of Innovation provides a framework for understanding the differential use of substances and subsequent decline. Financial support: Fundingwasprovidedbygrants fromSoutheast Michigan Community Alliance and the state of Michigan (Lycaki-Young funds).

Safety monitoring of ophthalmic biologics: a systematic review of pre- and postmarketing safety data.

The present study evaluates the safety of the biologics approved for the treatment of ocular diseases. The European medicines agency Website was searched to identify biologics with approved ophthalmologic therapeutic indications. A systematic search was performed using MEDLINE, the Cochrane Central Register of Controlled Trials (CENTRAL) and the International Clinical Trials Registry Platform up to December 2013. Pre-marketing, phase III randomized controlled trials (RCT), postmarketing clinical trials, observational longitudinal studies, and case reports involving adverse events (AE) were included. Methodological quality was assessed by Downs & Black checklist. All European spontaneous reports of AE included in the Eudravigilance up to December 2013 were also considered. AE were classified as ocular (related and non-related with the injection procedure) and non-ocular (related or non-related with vascular endothelial growth factor inhibition). Incidences of all reported AEs were estimated. Pegaptanib, ranibizumab, and aflibercept were identified as ophthalmic biologics. Fourteen premarketing RCT, 7 postmarketing clinical trials, 31 observational studies, along with 31 case reports and 7,720 spontaneous reports were identified and included in this study. Both in pre- and postmarketing settings, ocular AEs were more frequent than non-ocular AEs. Premarketing safety data inform the most common AEs. Postmarketing studies suggest an increased number of events such as retinal pigmented epithelium tears (0.6%-24%), thromboembolic events (0.8%-5%), and mortality (2.8%-4%). This study highlights the need to properly evaluate the risk for rare, serious, and long-term AEs, such as thromboembolic events, since they can lead to imbalances in the benefit-risk ratio of biologics in ophthalmology.

Reductions in reported deaths following the introduction of extended-release oxycodone (OxyContin) with an abuse-deterrent formulation.

PurposeAbuse of opioid analgesics for their psychoactive effects is associated with a large number of fatalities. The effect of making opioid tablets harder to crush/dissolve on opioid-related fatalities has not been assessed. The objective of this study was to assess the impact of introducing extended-release oxycodone (ERO [OxyContin®]) tablets containing physicochemical barriers to crushing/dissolving (reformulated ERO) on deaths reported to the manufacturer.MethodsAll spontaneous adverse event reports of death in the US reported to the manufacturer between 3Q2009 and 3Q2013 involving ERO were used. The mean numbers of deaths/quarter in the 3 years after reformulated ERO introduction were compared with the year before. Changes in the slope of trends in deaths were assessed using spline regression. Comparison groups consisted of non-fatal reports involving ERO and fatality reports involving ER morphine.ResultsReports of death decreased 82% (95% CI: −89, −73) from the year before to the third year after (131 to 23 deaths per year) reformulation; overdose death reports decreased 87% (95% CI: −93, −78) and overdose deaths with mention of abuse-related behavior decreased 86% (95% CI:−92, −75). In contrast, non-fatal ERO reports did not decrease post-reformulation, and reported ER morphine fatalities remained unchanged. The ratio of ERO fatalities to all oxycodone fatalities decreased from 21% to 8% in the year pre-reformulation to the second year post-reformulation.ConclusionsThese findings, when considered in the context of previously published studies using other surveillance systems, suggest that the abuse-deterrent characteristics of reformulated ERO have decreased the fatalities associated with its misuse/abuse. © 2014 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd.

SAT0479 Early Findings from Prolia® Post-Marketing Safety Surveillance for Atypical Femoral Fracture, Osteonecrosis of the Jaw, Severe Symptomatic Hypocalcemia, and Anaphylaxis

BackgroundProlia has marketing authorization in the EU, US, Canada, Japan, and over 40 countries or administrative districts worldwide for the treatment of postmenopausal women with osteoporosis at high/increased risk for...