Systemic Adverse Drug Reactions Research Articles

Autoimmune diseases secondary to drug hypersensitivity syndrome

Drug hypersensitivity syndrome, also called drug reaction with eosinophilia and systemic symptoms (DRESS syndrome) , is a severe systemic adverse drug reaction usually caused by exposure to specific drugs. Several reports have shown that after remission of DRESS syndrome, some patients developed autoimmune diseases, such as type-1 diabetes mellitus, Grave's disease, Hashimoto's thyroiditis, lupus erythematosus, sjogren syndrome, vitiligo, graft-versus host disease (GVHD) and other diseases. However, the exact pathogenesis of these autoimmune diseases remains unclear, and mainly involves regulatory T cell dysfunction, virus infection and autoantibody production. This review mainly summarizes DRESS syndrome-related autoimmune diseases and their pathogenesis. Key words: Drug eruptions; Autoimmune diseases; Eosinophilia; Autoantibodies; Drug-induced hypersensitivity syndrome

European Medicines Agency new adverse drug reactions system to go live in November

European Medicines Agency new adverse drug reactions system to go live in November

PCV1 - Systemic Adverse Drug Reactions of Antihypertensive Agents

PCV1 - Systemic Adverse Drug Reactions of Antihypertensive Agents

Consumer reporting of adverse drug reactions: Systems that allow patients to report side effects of the drugs they are taking have yielded valuable information for improving drugs safety and health care.

Consumer reporting of adverse drug reactions: Systems that allow patients to report side effects of the drugs they are taking have yielded valuable information for improving drugs safety and health care.

Adverse drug reaction monitoring of newer oral anti-diabetic drugs - A pharmacovigilance perspective

Objective: To monitor and evaluate adverse drug reactions (ADRs) of newer oral anti-diabetic drugs in type II diabetics by spontaneous/solicited ADR monitoring. Material and methods: Two hundred and thirty two diabetic patients on newer oral antidiabetic drugs were evaluated prospectively in a cross-sectional study over a period of eighteen months. All patients were followed up for ADRs which were evaluated for incidence, frequency, severity and causality. ADR severity was graded according to University of Virginia Health System Adverse Drug Reaction Reporting program criteria and causality assessment was done using WHO-UMC scale. Results: 190 out of 232 patients (42 patients lost to follow up) were evaluated. ADRs were observed in 34 cases (17.9%). Most common ADRs were gastrointestinal (44.2%) followed by musculoskeletal (17.6%), metabolic (14.7%), infections (5.9%) and others (17.6%). The maximal frequency of ADRs was seen with sitagliptin (6.4%) followed by vildagliptin(3.8%), saxagliptin(2.7%), saroglitazar(2.1%), linagliptin(1.6%), canagliflozin(1.6%). 25(73.5%), 8(23.5%) and 1(3%) ADRs were mild, moderate and severe respectively. 24(70%) ADRs were classified as possible, 9(27%) probable and 1(3%) unlikely on causality assessment. Conclusion : Newer oral antidiabetic drugs like gliptins and SGLT-2 inhibitors have potential to cause ADRs. Gastro-intestinal, musculoskeletal, metabolic were most common ADRs. Active pharmacovigilance should be carried out for risk identification and management.

Pharmacovigilance in radiopharmaceuticals.

Indian Pharmacopoeia Commission is Committed for maintaining the standards of drugs including Radiopharmaceuticals (RPs) by publishing Indian Pharmacopoeia. These RPs are being used in India for diagnostic or therapeutic purpose. RPs though contain relatively small quantities of active ingredient and administered in small volumes could cause some adverse reactions to the patients. The objective of presenting this article is to introduce the system of adverse drug reaction reporting to the nuclear medicine fraternity who are dealing with RPs.

Pharmacovigilance in Cabo Verde: Measuring the Impact of Pharmacovigilance Educational Campaign o,n Consumer’s Knowledge

Background: A monitoring system of adverse drug reactions is vital to patient safety and patients should have an active role in it. However, encouraging consumer involvement in their healthcare requires that they are or can be sufficiently well informed to make rational decisions. Therefore, mass education campaigns can be important to promote public education about medicines. Purpose: To assess the impact of an educational campaign to promote knowledge of consumer regarding use of medicines. Methods: A descriptive study was performed for consumer’s knowledge regarding rational use of medicine after a TV/radio campaign. A questionnaire was applied during 1 week (from 16 to 23 November 2015) in all urban areas of the capital of Cabo Verde to a population of 73,343. The data were analyzed using descriptive statistics and T-test. Results: The result reveals a general improvement on knowledge of consumer (p<0.0001) after the TV/radio educational program. For the two most sensitive issue of the first study, the results indicate an improvement of 0.7 percentage points for medicine-risk perception and an increase of 11.6 percentage points for the perception of quality of generics. Conclusion: Educational campaigns for consumer on the appropriate use of medicines are of crucial importance and well-tailored campaigns can improve the general knowledge, especially by addressing the campaign through the healthcare professional. It is recommended to continue the transmission and amplification of the TV/radio program.

Estimation of the Dose-Dependency of Systemic Adverse Drug Reactions during the Subtherapeutic Administration of Various Drugs

Estimation of the Dose-Dependency of Systemic Adverse Drug Reactions during the Subtherapeutic Administration of Various Drugs

Common data model for decision support system of adverse drug reaction to extract knowledge from multi-center database

An adverse drug reaction (ADR) surveillance system integrated with various electronic medical record (EMR) systems has been suggested as an effective way to collect more data and analyze ADRs earlier than the spontaneous reporting of ADRs. Because Korean hospitals have heterogeneous EMR databases, a common data model (CDM) should first be defined to develop the multi-center EMR-based drug surveillance system. We investigated the data models from two prominent drug safety surveillance studies, the Mini-Sentinel program and the Observational Medical Outcomes Partnership, and developed an EMR-based ADR common data model (EADR CDM). The EADR CDM has eight tables, including a demographic table, drug table, visit table, procedure table, diagnosis table, death table, laboratory table and organization table. Each table consists of 5---12 fields. Among a total of 2,931,060 patients from January 2008 to December 2012 in clinical data warehouse of the S hospital, we extracted the data from 135,745 patients who were prescribed below drugs to determine whether the exported data were sufficient to detect ADRs of six drugs. After validation, we found that the transformed data based on EADR CDM is helpful to understand the prescription pattern and explore feasible medication list for adverse drug signal detection. The collection of diverse data using the CDM is an effective method of early decision of ADRs. This study provides guidelines for developing the CDM and plans to develop the drug safety surveillance system based on multi-center EMR.

5% Lidocaine Medicated Plaster for the Treatment of Postherpetic Neuralgia: A Review of the Clinical Safety and Tolerability.

Postherpetic neuralgia (PHN) is a common, very painful, and often long-lasting complication of herpes zoster which is frequently underdiagnosed and undertreated. It mainly affects the elderly, many of whom are already treated for comorbidities with a variety of systemic medications and are thus at high risk of drug–drug interactions. An efficacious and safe treatment with a low interaction potential is therefore of high importance. This review focuses on the safety and tolerability of the 5% lidocaine medicated plaster, a topical analgesic indicated for the treatment of PHN. The available literature (up to June 2014) was searched for publications containing safety data regarding the use of the 5% lidocaine medicated plaster in PHN treatment; unpublished clinical safety data were also included in this review. The 5% lidocaine medicated plaster demonstrated good short- and long-term tolerability with low systemic uptake (3 ± 2%) and minimal risk for systemic adverse drug reactions (ADRs). ADRs related to topical lidocaine treatment were mainly application site reactions of mild to moderate intensity. The treatment discontinuation rate was generally below 5% of patients. In one trial, the 5% lidocaine medicated plaster was better tolerated than systemic treatment with pregabalin. The 5% lidocaine medicated plaster provides a safe alternative to systemic medications for PHN treatment, including long-term pain treatment.Electronic supplementary materialThe online version of this article (doi:10.1007/s40122-015-0034-x) contains supplementary material, which is available to authorized users.

Factors that affect adverse drug reaction reporting among hospital pharmacists in Western China.

Hospital pharmacists can make a considerable contribution to the spontaneous reporting system of adverse drug reactions. The factors that influence adverse drug reaction reporting among hospital pharmacists remain largely unknown in China. This study aims to identify factors that affect hospital pharmacist-led adverse drug reaction reporting in Xi'an, and to obtain suggestions from pharmacists about how to improve the current adverse drug reaction reporting system. Hospital settings throughout Xi'an, a region of Western China. A matched case-control study was conducted on a population of 2,814 hospital pharmacists in Xi'an during 2011. Cases included all pharmacists who had reported at least one adverse drug reaction between 2008 and 2010 and agreed to participate in the study (186/204; 91.2 %); controls (n = 372) were pharmacists who had not reported any adverse drug reaction during the same period. A self-administered questionnaire was distributed to the participants. Logistic regression was performed to evaluate the association between indicator variables and the outcome of having reported at least one adverse drug reaction. Pharmacists' knowledge, attitude and practice towards adverse drug reaction reporting and factors affecting reporting. Higher professional title (adjusted OR 1.44; 95 % CI 1.07-1.94; p = 0.018), having received training about adverse drug reaction reporting (1.64; 1.04-2.57; p = 0.032), better knowledge about reporting (1.53; 1.12-2.08; p = 0.007), "lack of access to adverse drug reaction reporting form" (0.29; 0.12-0.72; p = 0.008) was independently associated with adverse drug reaction reporting. Clinical pharmacists were more likely to report an adverse drug reaction than dispensary pharmacists (1/adjusted OR 5.26; p < 0.001), pharmacy administrators (5.00; p = 0.003), and other technicians (5.56; p = 0.001). Higher professional title, having received training, mastering knowledge about reporting, and being a clinical pharmacist were positive predictors of pharmacist-led adverse drug reaction reporting. Lack of access to reporting forms was a negative predictor. Continuous training and establishing incentive mechanisms are needed to promote adverse drug reaction reporting among hospital pharmacists.

Filtering big data from social media – Building an early warning system for adverse drug reactions

ObjectivesAdverse drug reactions (ADRs) are believed to be a leading cause of death in the world. Pharmacovigilance systems are aimed at early detection of ADRs. With the popularity of social media, Web forums and discussion boards become important sources of data for consumers to share their drug use experience, as a result may provide useful information on drugs and their adverse reactions. In this study, we propose an automated ADR related posts filtering mechanism using text classification methods. In real-life settings, ADR related messages are highly distributed in social media, while non-ADR related messages are unspecific and topically diverse. It is expensive to manually label a large amount of ADR related messages (positive examples) and non-ADR related messages (negative examples) to train classification systems. To mitigate this challenge, we examine the use of a partially supervised learning classification method to automate the process. MethodsWe propose a novel pharmacovigilance system leveraging a Latent Dirichlet Allocation modeling module and a partially supervised classification approach. We select drugs with more than 500 threads of discussion, and collect all the original posts and comments of these drugs using an automatic Web spidering program as the text corpus. Various classifiers were trained by varying the number of positive examples and the number of topics. The trained classifiers were applied to 3000 posts published over 60days. Top-ranked posts from each classifier were pooled and the resulting set of 300 posts was reviewed by a domain expert to evaluate the classifiers. ResultsCompare to the alternative approaches using supervised learning methods and three general purpose partially supervised learning methods, our approach performs significantly better in terms of precision, recall, and the F measure (the harmonic mean of precision and recall), based on a computational experiment using online discussion threads from Medhelp. ConclusionsOur design provides satisfactory performance in identifying ADR related posts for post-marketing drug surveillance. The overall design of our system also points out a potentially fruitful direction for building other early warning systems that need to filter big data from social media networks.

System of adverse drug reactions reporting: What, where, how, and whom to report?

Sir, The continuous progress in medical and pharmaceutical sciences has made the availability of pharmaceutical products in the Indian market to prevent and control of several disease conditions. Irrespective of the benefits associated with the use of medicines adverse effects associated with them has emerged the challenges of monitoring Adverse Drug Reactions (ADRs) over large population base. World Health Organization (WHO) defined ADR as “A response which is noxious and unintended, and which occurs at doses normally used in humans for the prophylaxis, diagnosis, or therapy of disease, or for the modification of physiological function.”[1] To improve public health, the safe use of medicine must be monitored through an effective pharmacovigilance (PV) system. PV is defined as the science and activities relating to the detection, assessment, understanding and prevention of adverse effects, or any other possible drug-related problems.[2] Indian Pharmacopoeia Commission (IPC), Ghaziabad is functioning as a National Coordination Centre (NCC) for Pharmacovigilance Programme of India (PvPI). One Hundred and fifty ADR monitoring centres (AMCs) were established in various medical institutions/hospitals across India to monitor and collect ADR reports under NCC-PvPI.[3]

Identification of possible adverse drug reactions in clinical notes: The case of glucose-lowering medicines.

Objective:Through manual review of clinical notes for patients with type 2 diabetes mellitus attending a Danish diabetes center, the aim of the study was to identify adverse drug reactions (ADRs) associated with three classes of glucose-lowering medicines: “Combinations of oral blood-glucose lowering medicines” (A10BD), “dipeptidyl peptidase-4 (DDP-4) inhibitors” (A10BH), and “other blood glucose lowering medicines” (A10BX). Specifically, we aimed to describe the potential of clinical notes to identify new ADRs and to evaluate if sufficient information can be obtained for causality assessment.Methods:For observed adverse events (AEs) we extracted time to onset, outcome, and suspected medicine(s). AEs were assessed according to World Health Organization-Uppsala Monitoring Centre causality criteria and analyzed with respect to suspected medicines, type of ADR (system organ class), seriousness and labeling status.Findings:A total of 207 patients were included in the study leading to the identification of 163 AEs. 14% were categorized as certain, 60% as probable/likely, and 26% as possible. 15 (9%) ADRs were unlabeled of which two were serious: peripheral edema associated with sitagliptin and stomach ulcer associated with liraglutide. Of the unlabeled ADRs, 13 (87%) were associated with “other blood glucose lowering medications,” the remaining 2 (13%) with “DDP-4 inhibitors.”Conclusion:Clinical notes could potentially reveal unlabeled ADRs associated with prescribed medicines and sufficient information is generally available for causality assessment. However, manual review of clinical notes is too time-consuming for routine use and hence there is a need for developing information technology (IT) tools for automatic screening of patient records with the purpose to detect information about potentially serious and unlabeled ADRs.

Concentrated green tea extract induces severe acute hepatitis in a 63-year-old woman – A case report with pharmaceutical analysis

Etnopharmacological Relevance: The popularity of concentrated green tea extracts as dietary supplements for a wide range of applications is increasing due to their health-promoting effects attributed to the high amounts of catechins they contain. The most important of the green tea catechins is (−)-epigallocatechin-3-O-gallate (EGCG). While their beneficiary effects have been studied extensively, a small number of adverse events have been reported in the medical literature. Here we present a typical reversible course of severe hepatitis after green tea consumption. Materials and methodsThe case study describes in a 63-year old woman during treatment with green tea-capsules upon recommendation of a cancer support group. ResultsThe histological finding was consistent with drug induced hepatitis, and other possible causes of hepatitis were excluded. According to the CIOMS/RUCAM score the causality was assessed as “probable”. After discontinuation of medication, followed by extracorporal albumin dialysis, rapid and sustained recovery occurred. Pharmaceutically analysis (HPLC) of the green tea capsules did not give evidence for contaminants but revealed the two typical compounds of green tea, namely (−)-epigallocatechin-3-O-gallate (EGCG, 93.2%) and epicatechin (EC, 6.8%) at a very high dose level. ConclusionThe present case highlights the fact that such concentrated herbal extracts from green tea may not be free of adverse effects under certain circumstances. There is still a lack of a uniform European Union-wide surveillance system for adverse drug reactions of herbal products. Therefore this case underlines the importance of public awareness in the potential risks in use of herbal products.

Involvement of Anticancer Drugs in the Relief System for Adverse Drug Reactions in Japan

The compensation scheme for adverse drug reactions in Japan was implemented more than three decades ago as relief system by regulatory agencies. Because of the high frequency of adverse drug reactions, anticancer drugs have been excluded from coverage by the relief system since its implementation. Requests have recently been made by some patient advocates for the expansion of relief coverage to include anticancer drugs. In response to these requests, the Ministry of Health, Labor and Welfare of Japan established a committee to discuss relief from anticancer drug-induced health damages in June 2011. We conducted comprehensive research into the compensation scheme for adverse drug reactions in the world. We also investigated the situation of compensation and the committee for discussing inclusion of anticancer drugs into the relief system in Japan. Many countries including the United States and UK do not have relief or compensation schemes for no-fault compensation. We investigated whether a no-fault compensation system exists in Nordic countries (Sweden, Denmark, Norway and Finland), France, Germany, New Zealand and Taiwan in the world, although they offer different services from Japan. We also reviewed current situation and the fundamental difficulties associated with including anticancer drugs in the systems in Japan. The present study investigated the current situation and the fundamental difficulties associated with including anticancer drugs in the systems in Japan and pointed out part of the reason why the committee could not conclude involvement of anticancer drugs in the relief system.

Adverse Drug Reaction Labelling for Atomoxetine, Methylphenidate and Modafinil: Comparison of Product Information for Oral Formulations in Australia, Denmark and the United States

Objective Hyponatraemia is a serious adverse event commonly reported in elderly people treated with serotonergic antidepressants. The mechanism, incidence and risk factors for antidepressant induced hyponatraemia are not fully understood. Method In a retrospective chart analysis, depressed patients aged >63 years were investigated for change in serum sodium levels between two time points, separated by a median period of 45.5 days, with the first specimen taken prior to treatment. Patients were grouped into three cohorts; treated with an SSRI or SNRI (n=77), treated with an antidepressant other than an SSRI or SNRI (n=54) and not treated with an antidepressant (n=128). Results For change in sodium level between measurements and total number of patients with hyponatraemia, there was no significant difference between cohorts. However, the rate of reduction of serum sodium levels between time points was significantly greater for SSRI and SNRI treated patients (p<0.001) and patients treated with other antidepressants (p=0.03) compared to patients not treated with antidepressants. Moreover, the distribution of values of change in serum sodium was skewed towards reduced serum sodium in patients treated with SSRI or SNRIs (skew -0.43) and patients treated with other antidepressants (skew -0.09) but not for patients without antidepressants (skew 0.25). Conclusions These data suggest that antidepressant treatment is associated with hyponatraemia affecting a subgroup of individuals only. Generalised linear modelling showed that the risk of hyponatraemia increases with increased age, female gender, and particularly the antidepressant agents sertraline and escitalopram. The findings are of clinical significance as they demonstrate that hyponatraemia can occur rapidly with antidepressants, and SSRI/SNRI medications induce more rapid changes. They support the use of electrolyte monitoring early in antidepressant treatment in patients receiving antidepressants.

Phase III, randomized, double-blind, placebo-controlled trial of topical 2 % lidocaine for the prevention and treatment of oral mucosal pain in children

The aim of this study was to assess the efficacy in pain reduction of topical 2 % lidocaine compared to a placebo cream in children with oral mucosal lesions due to trauma or aphthous ulcers or in the prevention of clamp placement pain. The design was a double-blind, randomized, placebo-controlled, four-center trial on 64 patients. Pain intensity and relief were measured using a 100-mm visual analog scale (VAS). One-tailed Student's t test and ANOVA were used for statistical analyses. Independent of the pain origin, application of 2 % lidocaine cream led to a mean reduction in VAS pain intensity of 19.7 mm ± 18.3, which was significantly greater than that obtained with the placebo cream (p = .025). Analyses showed a statistically significant efficacy of the 2 % lidocaine cream (p < .0001). Its efficacy was not associated to any local or systemic adverse drug reaction, as reported by the patients. As the most important population represented in our patients was children whom a rubber dam clamp was placed, we also specifically analysed this population, and we were able to demonstrate a significantly greater efficacy of the 2 % lidocaine cream on the pain caused by the rubber dam clamp placement in comparison to the placebo cream (p < .005). A significant reduction in pain intensity occurred after application of 2 % lidocaine cream, and the effect was significantly greater than that obtained with the placebo cream. Considering the study's limitations, this product appears safe for use in children. For painful benign lesions of the oral mucosa (trauma or aphthous ulcers) or for preventing painful iatrogenic procedures such as rubber dam clamp placement, it is essential to treat or prevent pain onset, especially in the pediatric population for whom a painful experience could end in refusal of dental care. Application of a topical anesthetic in this specific situation is of particular interest, as is defining its efficacy and safety.

Drug-Induced Liver Injury Throughout the Drug Development Life Cycle: Where We Have Been, Where We are Now, and Where We are Headed. Perspectives of a Clinical Hepatologist

The subject of drug-induced liver injury (DILI) has been evolving for decades. While various guidance and other documents have been produced to help identify and manage DILI in the clinical trial setting, as well as the clinic, there are still many aspects of the process that remain incomplete. I have selected those aspects where guidance documents either do not cover all possible scenarios or where other recommendations are open to interpretation or where controversies still exist. The following discussion includes a number of these topics, including: when is it acceptable to continue development of a drug where hepatotoxicity is observed in animal models or other preclinical assessments? Should patients with underlying liver disease be routinely included in clinical trials? Are the current clinical and biochemical stopping rules for suspected DILI appropriate for all situations? Should we still be using fold elevations based on upper limits of normal or a subject’s own baseline values to assess the level of alanine aminotransferase or other liver-associated enzyme elevations? How can we best integrate the expanding fields of toxicogenomics, pharmacogenomics, metobolomics, proteomics and other new drug and host profiling into predicting DILI? Where do we stand with respect to a DILI biomarker to replace traditional liver associated enzymes? How do we improve upon the voluntary reporting system for adverse drug reactions? What are the most useful causality assessment methodologies to diagnose DILI and is it ever possible to exclude the drug in question? And how do we best determine and manage the competing benefits and risks of an agent causing DILI?

A Study of Community Pharmacists? Awareness and Contributions to Adverse Drug Reactions (ADRs) Reporting Systems in the Makkah, Kingdom of Saudi Arabia (KSA)

Introduction: Adverse Drug Reactions (ADRs) reporting is the cornerstone for any Pharmacovigilance system. The attitude and awareness towards ADRs reporting shows great variation among the health pharmacists and many factors influences the reporting of ADR. Aims and objective: To determine and evaluate awareness, knowledge and attitude of community pharmacists towards ADRs reported in the Makkah in Kingdom of Saudi Arabia (KSA). Materials and method: The present cross-sectional study was conducted by taking face to face interviews of 170 community pharmacists in Makkah. A prescribed questioner was used to collect basic information, professional information and knowledge about ADR reporting system and constrains in reporting ADR. Results: It was observed that all the participants were male and were of 23-30 yrs of age group. 88% of pharmacists were not having internet facility at their work place. Only 18% participants were aware of the ADR system. 56% of the respondents were not aware of the existence of the Saudi National Pharmacovigilance centre (NPC). According to 65% respondents the Ministry of Health (MOH) was responsible receiving and interpreting ADR reporting, whereas 65% of respondents considered the reporting of ADRs to be integral to this professional role as a pharmacist. The main factors that discouraged ADR reporting were the lack of reporting forms being available, that it was time consuming, that they did not know how to report them and some commented on their indifference to the system. Conclusion: The Community pharmacists could play an important role in ensuring the use of safe medications in patients. To achieve this aim more knowledge about the importance of reporting ADRs through appropriate training courses should be encouraged.