Adverse Drug Reports Research Articles

Infection rate in patients with psoriasis exposed to oral apremilast versus other oral agents (acitretin, cyclosporine, and methotrexate): A report from the RADAR (Research on Adverse Drug events And Reports) project

Infection rate in patients with psoriasis exposed to oral apremilast versus other oral agents (acitretin, cyclosporine, and methotrexate): A report from the RADAR (Research on Adverse Drug events And Reports) project

Rate of all infection for ustekinumab versus standard oral systemic therapeutic agents (acitretin, cyclosporine, or methotrexate) in the management of psoriasis: A report from the RADAR (Research on Adverse Drug events And Reports) project

Rate of all infection for ustekinumab versus standard oral systemic therapeutic agents (acitretin, cyclosporine, or methotrexate) in the management of psoriasis: A report from the RADAR (Research on Adverse Drug events And Reports) project

Chronic exposure to tetracyclines and association with subsequent nonmelanoma skin cancer: A report from the RADAR (Research on Adverse Drug events And Reports) project

Chronic exposure to tetracyclines and association with subsequent nonmelanoma skin cancer: A report from the RADAR (Research on Adverse Drug events And Reports) project

Malignant melanoma subsequent to natalizumab exposure: A report from the RADAR (Research on Adverse Drug events And Reports) project

Malignant melanoma subsequent to natalizumab exposure: A report from the RADAR (Research on Adverse Drug events And Reports) project

Investigating the Reasons for Failing to Report Adverse Drug Reactions (ADR) by Nurses of Neonatal Intensive Care Unit in the Year 2015

Investigating the Reasons for Failing to Report Adverse Drug Reactions (ADR) by Nurses of Neonatal Intensive Care Unit in the Year 2015

Hypomagnesemia and exposure to romidepsin: A Research on Adverse Drug events and Reports (RADAR) project.

e14072 Background: Romidepsin (R) is indicated for cutaneous T-cell lymphoma (CTCL) and peripheral T-cell lymphoma. Hypomagnesemia (HM) is common in these patients and is also listed in the Full Prescribing Information (FPI) for R. Moreover, since cardiac arrhythmias are associated with HM, patients exposed to R may be at higher risk. This study assessed whether HM was causally related to R exposure and to what extent magnesium (M) supplementation was undertaken in those with HM. Methods: We searched a large, U.S. patient data repository to detect all patients (aged 20-94 years) exposed to R (10/2010-01/2017). For these patients, serum M, as well as M supplementation data, was collected. Baseline M was assessed at initial R exposure, and HM was defined as either, a decline in M to < 1.8 mg/dL after R exposure or, in those with baseline M < 1.8 mg/dL, a decline in M by ≥0.1 mg/dL after R exposure. For each patient with HM after R exposure, the validated Naranjo Adverse Drug Reaction Probability Scale (NADRPS) was used to determine the probability that HM was caused by R. Results: Of 51 R-exposed CTCL (or other lymphoma) patients, 25 (49.0%) had HM. Of these 25, NADRPS scores yielded: 1 doubtful, 16 possible, 8 probable and 0 definite. Additionally, 24 of 25 patients with HM had documentation for presence or absence of M supplementation: 9 (37.5%) had supplementation with M agents considered to be bioavailable, 12 (50%) received M agents considered to have low bioavailability, and 3 (12.5%) had no M supplementation. Conclusions: In this study population, 25 of 51 (49.0%) patients had HM after R exposure, which appears to nearly double the percentage of patients described in the FPI. Moreover, 8 of 25 (32%) patients with HM had causality attributed to R exposure. In addition, 15 of 24 (63%) patients with HM received M supplementation with agents considered to have low bioavailability or received no M supplementation. These findings support the need for ongoing monitoring of R-exposed patients with low M, as well as the importance of repleting M with agents considered to be adequately bioavailable. Also, given that HM appears to be more frequent in this study population compared to pre-marketing data in the FPI, further studies are warranted.

In Silico Prediction of Drug-Induced Liver Injury Based on Adverse Drug Reaction Reports.

Drug-induced liver injury (DILI) is a major cause of drug attrition. Currently existing Quantitative Structure-Activity Relationship models have limited predictive capabilities for DILI. Furthermore, their practical applications were limited by lack of new hepatotoxicity data. In this study, we first collected and curated a novel set of 122 DILI-positive and 932 DILI-negative drugs from online adverse drug reports using proportional reporting ratios as the signal detection method. Second, three strategies (under-sampling the majority class, synthetic minority over-sampling technique, and adjusting decision threshold approach) were employed to develop predictive classification models to cope with the unbalanced dataset. Random forest (RF) models using CDK, MACCS, and Mold2 descriptors based on the under-sampling and over-sampling strategies afforded correct classification ratio (CCR) of ∼0.77 and 0.78, respectively. Recursive RF models based on the last strategy tremendously reduced modeling descriptors (at most 95.4% for Mold2) while apparently improved the predictability with a consensus CCR of 0.84 (sensitivity of 0.88 and specificity of 0.79). Structural analysis showed that pyrimidine derivatives, purine derivatives, and halogenated hydrocarbon were critical for drugs' hepatotoxicity. The reporting frequency of many drugs was gender-dependent (eg, antiviral and anti-cancer drugs for males and antibacterial drugs for females) as well as age-dependent (eg, antiviral and anti-cancer drugs for the middle age group of 20-29, 30-39, and 40-49). Approximately 84% of total cases were reported during the first 6 months of administration. The curated hepatotoxicity dataset along with the predictive classification models presented here should provide insight into future studies of DILI.

Study of adverse drug reactions in patients with diabetes attending a tertiary care hospital in New Delhi, India.

The present prospective observational study was carried out in a tertiary care hospital in New Delhi, India from May 2014 to June 2015 to report adverse drug reactions (ADRs) in patients with type 2 diabetes mellitus (T2DM) using antidiabetic drugs. A total of 220 patients (121 males, 99 females) were enrolled. ADRs were recorded on the prescribed form. Causality and severity assessment was done using Naranjo's probability scale and modified Hartwig and Siegel's severity scale, respectively. Commonly prescribed drugs were biguanides, peptide hormone and sulphonylurea. A total of 26 ADRs were recorded (16 in males and 10 in females). Most commonly observed ADRs were related to endocrine and gastrointestinal system. Severity assessment of ADRs showed seven (26.9%) ADRs as moderate, and 19 (73.1%) as mild. No severe reactions were observed. ADRs were mostly related to endocrine and gastrointestinal system. More information on prescribed drugs and their side effects is required for ensuring patient safety.

Hepatotoxicity with Vismodegib: An MD Anderson Cancer Center and Research on Adverse Drug Events and Reports Project.

BackgroundOn 30 January 2012, the US FDA approved vismodegib (Erivedge®, Genentech, CA, USA) for the management of both metastatic and locally advanced basal cell carcinoma.ObjectiveOur objective was to identify evidence of hepatotoxicity with vismodegib in the FDA Adverse Event Reporting System (FAERS) in treated patients in two National Cancer Institute Comprehensive Cancer Centers.MethodsFAERS was searched for reports dated 1 January 2009 through 31 December 2015 using terms including hedgehog pathway and vismodegib and hepatic-related terms such as liver, jaundice, and hepatitis, among others. Disproportionality analyses with estimates of proportional reporting ratio and empirical Bayesian geometric mean were conducted. A comprehensive literature review was conducted, and the clinical databases at the University of Texas MD Anderson Cancer Center and Robert H. Lurie Comprehensive Cancer Center of Northwestern University were searched.ResultsTwo cases of severe liver dysfunction were published (Common Terminology Criteria for Adverse Events [CTCAE] class III), and 94 reports of adverse events (AEs) were detected in FAERS, 35 of which were serious AEs. Safety notifications related to hepatotoxicity have not been issued by the manufacturer or the FDA, although vismodegib is listed in LiverTox and the European Medicines Agency website.ConclusionWe identified a detectable safety signal for hepatotoxicity for vismodegib within 4 years of FDA approval. Vismodegib should be used in patients with severe liver disease only after careful consideration, and concomitant hepatotoxic medications should be avoided. Rapid dissemination of such safety concerns is expected to result in fewer serious hepatotoxic AEs and more optimal outcomes for patients with cancer receiving vismodegib.Electronic supplementary materialThe online version of this article (doi:10.1007/s40268-016-0168-2) contains supplementary material, which is available to authorized users.

Effectiveness of pharmacovigilance: multifaceted educational intervention related to the knowledge, skills and attitudes of multidisciplinary hospital staff

OBJECTIVES:Most educational interventions in pharmacovigilance are designed to encourage physicians to report adverse drug reactions. However, multidisciplinary teams may play an important role in reporting drug-related problems. This study assessed the impact of a multifaceted educational intervention in pharmacovigilance on the knowledge, skills and attitudes of hospital professionals.METHOD:This prospective, open-label, non-randomized study was performed in a medium-complexity hospital in São Paulo, Brazil. The intervention involved four activities: 1) an interactive lecture, 2) a practical class, 3) a pre-post questionnaire administered to professionals on a multidisciplinary team, and 4) educational material. The intervention’s impact on the professionals’ knowledge and skills was assessed using the World Health Organization’s definitions. The intervention’s effect on the professionals’ attitudes was analysed by the prevalence of adverse drug event reports (adverse drug reactions, medication errors, therapeutic failure and drug quality deviations) and the relevance (seriousness and expectancy) of the events.RESULTS:One hundred seventy-three professionals were enrolled. A 70-fold increase in the number of adverse drug event reports was observed during the 12 months post-intervention. The intervention improved the professionals’ form-completion skills (p<0.0001) and their knowledge of pharmacovigilance (p<0.0001). The intervention also contributed to detecting serious drug-induced events. The nursing staff reported medication errors, and pharmacists and physiotherapists recognized serious adverse drug reactions. Physicians communicated suspicions of therapeutic failure.CONCLUSIONS:A multidisciplinary approach to drug-safety assessments contributes to identifying new, relevant drug-related problems and improving the rate of adverse drug event reporting. This strategy may therefore be applied to improve risk communication in hospitals.

Factors that Motivate Healthcare Professionals to Report Adverse Drug Events: A Systematic Review

The underreporting of adverse drug events (ADEs) is an important issue that affects the evaluation of the risk/benefit profile of drugs, with the potential for major impact on public health, such as undermining market regulation of drugs and reducing patient safety. The objective of this systematic review was to identify and categorize the factors that motivate ADE reporting by healthcare professionals. A systematic review was conducted, based on the PRISMA guidelines, in the PubMed, Scopus, LILACS and SciELO databases, for studies published up to 30 November 2015. A search strategy was designed to identify published studies that evaluated factors that motivate professionals to report adverse events. Factors that were identified as influencing ADE reporting were subsequently categorized by the authors, to reveal common themes that might be used to improve ADE reporting rates. There were 410 potentially relevant studies identified, of which 133 were duplicates and 234 did not meet the inclusion criteria at initial screening. After reading in full, a further 15 articles were eliminated and 28 articles were included in the systematic review. It was observed that the majority of studies mainly contemplated pharmacists (n = 16) and physicians (n = 16). The seven major categories that motivate ADE reporting by health professionals are: knowledge of the ADE, incentives, notification methods, educational intervention, risk management, educational materials, and professional responsibility. Factors that motivate healthcare professional to report ADEs can be classified into seven common themes. It is likely that multiple categories will need to be addressed as part of ongoing continuing education programs to increase motivation for ADE reporting by healthcare professionals.

Drug-induced progressive multifocal leukoencephalopathy: a case/noncase study in the French pharmacovigilance database.

Progressive multifocal leukoencephalopathy (PML) is an often fatal demyelinating disease of the central nervous system. As effective treatment is unavailable, identification of all drugs that could be associated with PML is essential. The objective of this study was to investigate the putative association of reports of PML and drugs. We used the case/noncase method in the French PharmacoVigilance database (FPVD). Cases were reports of PML in the FPVD between January 2008 and December 2015. Noncases were all other reports during the same period. To assess the association between PML and drug intake, we calculated an adverse drug report odds ratio (ROR) with its 95% confidence interval. We have studied the delay of onset of PML for each drug concerned. Among the 101 cases of PML, 39 drugs were mentioned as suspect. The main therapeutic classes suspected with significant ROR were antineoplastic agents (n = 85), immunosuppressants (n = 67), and corticosteroids. A latent interval from the time of drug initiation to the development of PML is established: the median time to onset was 365 days (123-1095 days). The onset of PML is highly variable and differs among drug classes [from 1 to 96 months (IQR: 39.0-126)]. An association between PML and some immunosuppressant drugs was found as expected, but also with antineoplastic agents and glucocorticoids. An important delay of PML onset after stopping treatment is suspected and should alert prescribers. Prescribers but also patients should be informed about the potential associations with all these drugs. Monitoring could be necessary for many drugs to early detect PML.

Identifying Drug–Drug Interactions by Data Mining

Background— Knowledge about drug–drug interactions commonly arises from preclinical trials, from adverse drug reports, or based on knowledge of mechanisms of action. Our aim was to investigate whether drug–drug interactions were discoverable without prior hypotheses using data mining. We focused on warfarin–drug interactions as the prototype. Methods and Results— We analyzed altered prothrombin time (measured as international normalized ratio [INR]) after initiation of a novel prescription in previously INR-stable warfarin-treated patients with nonvalvular atrial fibrillation. Data sets were retrieved from clinical work. Random forest (a machine-learning method) was set up to predict altered INR levels after novel prescriptions. The most important drug groups from the analysis were further investigated using logistic regression in a new data set. Two hundred and twenty drug groups were analyzed in 61 190 novel prescriptions. We rediscovered 2 drug groups having known interactions (β-lactamase-resistant penicillins [dicloxacillin] and carboxamide derivatives) and 3 antithrombotic/anticoagulant agents (platelet aggregation inhibitors excluding heparin, direct thrombin inhibitors [dabigatran etexilate], and heparins) causing decreasing INR. Six drug groups with known interactions were rediscovered causing increasing INR (antiarrhythmics class III [amiodarone], other opioids [tramadol], glucocorticoids, triazole derivatives, and combinations of penicillins, including β-lactamase inhibitors) and two had a known interaction in a closely related drug group (oripavine derivatives [buprenorphine] and natural opium alkaloids). Antipropulsives had an unknown signal of increasing INR. Conclusions— We were able to identify known warfarin–drug interactions without a prior hypothesis using clinical registries. Additionally, we discovered a few potentially novel interactions. This opens up for the use of data mining to discover unknown drug–drug interactions in cardiovascular medicine.

The Relationship between Psychotropic Drug Use and Suicidal Behavior in Japan: Japanese Adverse Drug Event Report.

Introduction: Very few studies have explored the adverse effect of psychotropic drugs worldwide. Methods: This study analyzed 1 813 suicide-related drug reports involving 553 patients collected from the Japanese National Adverse Drug Report Database between October 2001 and January 2012 to investigate psychotropic drugs associated with completed suicide vs. other suicide-related behaviors, including ideation and self-injury. The drugs investigated included antidepressants, antipsychotics, benzodiazepines, non-benzodiazepine hypnotic agents, noradrenergic and specific serotonergic antidepressants, selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, and other drugs. Results: These reports referenced 300 (54.2%) individuals who completed suicide. Adjusting for age, sex, and drugs used, the multivariate model revealed that participants who took antipsychotics were 1.70 times (95% CI, 1.11-2.61) more likely to complete suicide compared with those who did not. All other drugs became non-significant. Compared with those who took only one medication, those prescribed more than 4 drugs were more likely to complete suicide (OR 4.44, 95% CI, 2.40-8.20). Discussion: Antipsychotic drugs and polypharmacy may be regarded as predictors of completed suicide.

TOLVAPTAN USE IN SEVERE NEONATAL AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE (ADPKD): THE PHARMACEUTICAL CHALLENGE

BackgroundUnlicensed medications are used all the time in the management of diseases in childhood. Tolvaptan (Jinarc®) is a vasopressin V2-receptor antagonist licensed for use to slow the progression of cyst...

Nystatin and miconazole: pharmacological and clinical evidence regarding interactions with warfarin.

A retrospective case series published in 2012 concluded that miconazole and nystatin used as topical antifungal drugs appear to interact equally strongly with warfarin. If confirmed, this finding has significant implications for clinical practice. This study evaluates the evidence. Evidence from the pharmacology literature, the medical literature and the 'yellow card' adverse drug reaction surveillance reports was analysed regarding possible interactions of nystatin and miconazole with warfarin. There is strong evidence to support the derangement of warfarin anticoagulation by miconazole oral gel in all areas of evidence studied. No postulated mechanism of interaction, no additional published reported cases and no supportive data from adverse drug reports were identified which would corroborate the case for a significant interaction between nystatin and warfarin. Miconazole and nystatin used as topical antifungal drugs do not interact equally strongly with warfarin. Miconazole oral gel can clearly interact with warfarin to cause derangement of anticoagulation. Nystatin appears unlikely to interact with warfarin.

Serious adverse drug reactions to zolpidem: does impaired metabolic clearance and concurrent SSRI/SNRI use increase risk?

AbstractZolpidem is one of the most commonly used drugs for insomnia but it has been associated with adverse neuropsychiatric effects and complex sleep‐related behaviours. In this report, the pharmacokinetics, pharmacodynamics and putative serious adverse drug reactions (ADRs) to zolpidem are briefly described. Nine ‘hypothesis generating’ cases from a psychiatry practice are presented to suggest that in cytochrome P450 poor metabolisers, inhibitory metabolic drug–drug interactions and pharmacodynamic synergies with selective serotonin reuptake inhibitor/serotonin‐noradrenaline reuptake inhibitor antidepressants may increase the risk of serious ADRs to zolpidem.

Melanoma in men treated with PDE5A inhibitors: A report from the RADAR (Research on Adverse Drug Events And Reports) project

Melanoma in men treated with PDE5A inhibitors: A report from the RADAR (Research on Adverse Drug Events And Reports) project

Association of melanoma and nonmelanoma skin cancer with antihypertensive drugs: A report from the Research on Adverse Drug events And Reports project

Association of melanoma and nonmelanoma skin cancer with antihypertensive drugs: A report from the Research on Adverse Drug events And Reports project

Profile of rheumatology patients willing to report adverse drug reactions: bias from selective reporting.

BackgroundAdverse drug reactions (ADRs) have a significant impact on human health and health care costs. The aims of our study were to determine the profile of rheumatology patients willing to report ADRs and to identify bias in such a reporting system.MethodsSemi-intensive ADRs reporting system was used in our study. Patients willing to participate (N=261) completed the questionnaire designed for the purpose of the study at the hospital admission. They were subsequently classified into two groups according to their ability to identify whether they had experienced ADRs during the previous month. Group 1 included 214 out of 261 patients who were able to identify ADRs, and group 2 consisted of 43 out of 261 patients who were not able to identify ADRs in their recent medical history.ResultsGroup 1 patients were more significantly aware of their diagnosis than the patients from group 2. Marginal significance was found between rheumatology patients with and without neurological comorbidities regarding their awareness of ADRs. The majority of patients reported ADRs of cytotoxic drugs. The most reported ADRs were moderate gastrointestinal discomforts.ConclusionWe may draw a profile of rheumatological patients willing to report ADRs: 1) The majority of them suffer from systemic inflammatory diseases and are slightly more prone to neurological comorbidities. 2) They are predominantly aware of their diagnosis but less able to identify the drugs that may cause their ADRs. 3) They tend to report mainly moderate gastrointestinal ADRs; that is, other cohorts of patients and other types of ADRs remain mainly undetected in such a reporting, which could represent a bias. Counseling and education of patients as well as developing a network for online communication might improve patients’ reporting of potential ADRs.