Risk Of ADRs Research Articles

New restrictions for alemtuzumab due to risk of serious ADRs

New restrictions for alemtuzumab due to risk of serious ADRs

Do the 2015 Beers Criteria predict medication‐related harm in older adults? Analysis from a multicentre prospective study in the United Kingdom

To investigate whether inappropriate prescribing, defined by the Beers Criteria, is associated with medication-related harm (MRH), hospital admission, and mortality in older adults in England. A multicentre, prospective cohort study recruited 1280 patients (median age 82 years) at hospital discharge. Patients were followed-up in the community by pharmacists for 8 weeks to identify MRH (harm from adverse drug reactions, non-adherence, and medication errors) and hospital admissions. One-year mortality was determined using hospital records. Potentially inappropriate medications (PIMs) were determined using the 2015 version of the Beers criteria. Logistic regression was used to investigate the relationship between patients prescribed PIMs and adverse outcomes. Two hundred and seventy-six patients (22%) were prescribed one or more PIMs at hospital discharge. The main PIM classes prescribed at hospital discharge were benzodiazepines and related drugs (30%) and antidepressants (27%). 1116 out of 1280 patients completed follow-up and 413 (37%) experienced MRH. In 51 cases (12%), MRH was attributable to a PIM. There was no significant relationship between patients prescribed PIMs and overall MRH, hospital readmission or all-cause one-year mortality. Multiple PIMs at discharge was independently associated with an increased risk of ADR (OR 2.32, 95% CI 1.03-5.23). The prescribing of PIMs is common at hospital discharge of older adults in England. The 2015 Beers criteria have a limited clinical value to predict adverse outcomes following hospital discharge in this setting.

Greater risk of ADRs, hospitalisation with PIMs in elderly

Greater risk of ADRs, hospitalisation with PIMs in elderly

Genotype-Guided Thiopurine Dosing Does not Lead to Additional Costs in Patients With Inflammatory Bowel Disease.

Background and AimsDecreased thiopurine S-methyltransferase [TPMT] enzyme activity increases the risk of haematological adverse drug reactions [ADRs] in patients treated with thiopurines. Clinical studies have shown that in patients with inflammatory bowel disease [IBD], pharmacogenetic TPMT-guided thiopurine treatment reduces this risk of ADRs. The aim of this study was to investigate whether this intervention impacts on healthcare costs and/or quality of life.MethodsAn a priori defined cost-effectiveness analysis was conducted in the Thiopurine response Optimization by Pharmacogenetic testing in Inflammatory bowel disease Clinics [TOPIC] trial, a randomized controlled trial performed in 30 Dutch hospitals. Patients diagnosed with IBD [age ≥18 years] were randomly assigned to the intervention [i.e. pre-treatment genotyping] or control group. Total costs in terms of volumes of care, and effects in quality-adjusted life years [QALYs], based on EuroQol-5D3L utility scores, were measured for 20 weeks. Mean incremental cost savings and QALYs with confidence intervals were calculated using non-parametric bootstrapping with 1000 replications.ResultsThe intervention group consisted of 381 patients and the control group 347 patients. The mean incremental cost savings were €52 per patient [95% percentiles −682, 569]. Mean incremental QALYs were 0.001 [95% percentiles −0.009, 0.010]. Sensitivity analysis showed that the results were robust for potential change in costs of screening, costs of biologicals and costs associated with productivity loss.ConclusionsGenotype-guided thiopurine treatment in IBD patients reduced the risk of ADRs among patients carrying a TPMT variant, without increasing overall healthcare costs and resulting in comparable quality of life, as compared to standard treatment.

A study of serious adverse drug reactions with antiepileptic drugs: a pharmacovigilance study

Background: Approximately 50 million people worldwide have epilepsy, making it one of the most common neurological diseases globally. There are currently more than 25 drugs in the market for the treatment of epilepsy, many of which have similar efficacy but differ in their tolerability profile. Besides unmatched beneficial potential of antiepileptic drugs, it is associated with many adverse reactions too. This study aims to identify the serious adverse reactions caused by prescribed antiepileptics, reported at the pharmacovigilance centre of government tertiary care centre.Methods: This is a retrospective, pharmacovigilance study of the antiepileptic drugs adverse reactions reported over a period of 1 year at a tertiary care centre.Results: A total of 120 ADRs of antiepileptic drugs were reported and collected at the pharmacovigilance centre. According to the WHO-ART system organ classification of ADRs, 78% of ADRs belonged to skin and appendages disorder. Based on the modified Hartwig and Siegel scale of severity, 60.8% ADRs were mild, 18.5% were moderate and 20.8 % were severe ADRs. The severe ADRs included: Steven-Johnson syndrome, Toxic epidermal necrolysis, Erythroderma, DRESS syndrome and Acute pancreatitis. Phenytoin has been found to be the antiepileptic drug causing the most number of severe ADRs amongst the prescribed antiepileptics. According to the modified Schumock and Thornton criteria most of the severe ADRs were not preventable.Conclusions: This study analyses the ADRs associated with antiepileptics reported at the pharmacovigilance centre. 20.8% ADRS were severe, this indicates that the epileptic patients should be closely monitored for ADRs, to avoid clinically significant harmful consequences. The awareness of ADRs would help physicians to identify patients with greater risk of ADRs and therefore, might benefit from ADRs monitoring and reporting programmes.

Antipsychotics use: 2006-2013 trends in prevalence and incidence and characterization of users.

The present study was conducted to describe antipsychotic (AP) prevalent and incident use, characteristics of AP users, and their trends in the French population. A cross-sectional study was repeated yearly from January 1, 2007 to December 31, 2013 (for prevalence analysis) or to December 31, 2012 (for incidence analysis) using the French Health Insurance reimbursement database (Echantillon Généraliste de Bénéficiaires, EGB). For each year studied, prevalent and incident AP users were described in terms of age and gender overall, and according to the type of AP (FGAPs or SGAPs) used at index date. In addition, concurrent medications and comorbidities that a priori contraindicate the use of drugs having atropinic properties were researched. Prevalence and incidence remained relatively stable along the 2007-2013 period. Trends slightly decreased, from 2.07% (n = 10,252) to 2.05% (n = 11,015) for prevalence, and from 0.73% (n = 3461) to 0.66% (n = 3363) for incidence, especially in elderly, in contrast of children and adolescents (+ 39% for prevalence, from 184 to 271). The number of coprescribed drugs was found high (median = 5) and remained constant over time. In 2013, about 7% of prevalent AP users presented with a comorbidity increasing the risk of atropinic ADRs, and 36% used at least one concurrent atropinic drug. In incident AP users, these numbers were of 8 and 29%, respectively. The present study highlighted a marked shift from FGAPs toward SGAPs, as well as an increase in AP use in children and adolescents in France.

Exposure to anticholinergic and sedative medicines as indicators of high-risk prescriptions in the elderly.

Background There are several assessment scales to evaluate the risk of falls or the adverse drug reaction risk. Few are sufficiently specific to assess the impact of drug prescriptions on falls in geriatric populations. Objective To define the risk of anticholinergic and sedation-related ADRs in an elderly hospitalized patient population using the Drug Burden Index (DBI), Anticholinergic Drug Scale (ADS), andSedative Load Model (SLM). Setting Five geriatric university hospital centersin France. Method Multicenter prospective cohort study from 2011 to 2013. Drug prescriptions were compiled to estimate anticholinergic and sedative exposure. Any associations between the drug scales and falls were assessed. Main outcome measure Drug exposure estimated with the DBI, ADS, and SLM scales. Results 315 patients, with a mean age of 87years and 117 documented falls, were included from 5 geriatric hospitals. Sixty-one percent of these patients had a DBI>0, 20.3% had an ADS≥3, 56.2% a SLM>0. No association was detected between the scores and the risk of a fall (p>0.05). Factors significantly associated with a risk of a fall were: a prior history of a fall in the previous 12months (adjusted odds ratio [aOR]=7.24, 4.06-12.89), orthostatic hypotension ([aOR]=2.84; 1.39-5.79), or prescription of antidepressants ([aOR]=2.12; 1.17-3.84). Conclusion A specific scale to identify high-risk prescriptions would help clinicians and pharmacists to optimize therapeutic treatments for the elderly. In light of the multifactorial characteristics of falls, predicting their risk should be based on a well-defined set of factors.

An Intensive Monitoring of Adverse Drug Reactions among Elderly Patients Hospitalized in Medical Wards of a Tertiary Care Hospital

<p style="text-align: justify;"><strong>Objective:</strong> To evaluate the pattern of adverse drug reactions in elderly patients hospitalized in medical wards at a tertiary care hospital in India. <strong>Methods:</strong> Elderly patients&ge;60 years hospitalized in three randomly selected medical units were enrolled and followed up daily till discharge. Detailed information of patients and ADRs were recorded by interviewing patients, doctors and nurses. Appropriateness of drug treatment in patients&ge;65 years was analyzed using Beer&rsquo;s criteria. ADRs were assessed for incidence, onset, duration, management, outcome, causality, severity, preventability, seriousness and risk factors. <strong>Results:</strong> A total of 1017 patients were enrolled (mean age: 69.5&plusmn;7.6 years); majority (80.9%) suffered from &gt;1 ailments. Patients received 6.3&plusmn;0.5 drugs, commonly by oral (48%) and intravenous (41.6%) routes. Inappropriate drug therapy was observed in 76 patients of &ge;65 years. ADRs were observed in 107(10.7%) patients, majority occurred within first week, commonly affected GI (29.9%), central and peripheral nervous system (17.8%) and were frequently associated with antimicrobials (44.2%), drugs acting on CVS (13.3%) and endocrine systems (12.5%). Majority of reactions were mild (55.1%), non-serious (73.8%), not preventable (85.9%), recovered completely at discharge (87.8%) and had possible causal association with suspect drug (68.2%). Age&gt;80 years, &ge;3 diseases, prescription of &gt;10 drugs and hospitalization for&gt;4 days were risk factors for occurrence of ADRs. <strong>Conclusion:</strong> Adverse reactios are common in elderly and were frequently affect gastrointestinal, central and peripheral nervous systems. Reactions are mild, non-serious and commonly caused by antimicrobials and drugs acting on cardiovascular or endocrine systems. Multiple diseases, polytherapy, age&gt;80 years and hospitalization&gt;4 days increase the risk of ADRs. <p style="text-align: justify;"><strong>Key words:</strong> Intensive Monitoring, Elderly Patients, Medical Inpatients, Tertiary Care, Risk Factors.

Adverse drug reactions during drug-resistant TB treatment in high HIV prevalence settings: a systematic review and meta-analysis.

To estimate the prevalence of adverse drug reactions or events (ADR) during drug-resistant TB (DR-TB) treatment in the context of settings with high HIV prevalence (at least 20% of patients). We conducted a systematic review and meta-analysis of articles in PubMed and Scopus. Pooled proportions of patients experiencing adverse events and relative risk with 95% CI were calculated. The search yielded 24 studies, all observational cohorts. Ten reported on the number of patients experiencing ADR and were included in the meta-analysis representing 2776 study participants of whom 1943 were known to be HIV infected (70.0%). An average of 83% (95% CI: 82%-84%) of patients experienced one or more ADR. Among the seven articles ( n = 664 study participants) with information on occurrence of severe ADR, 24% (95% CI: 21%-27%) of patients experienced at least one severe ADR during drug-resistant TB treatment. Sixteen of the 24 studies analysed the relative risk of ADR by HIV infection, nine of which found no statistically significant association between HIV infection and occurrence of drug-related ADR. There was insufficient information to disaggregate risk by concomitant treatment with HIV antiretrovirals or by immunosuppression (CD4 count). No randomized clinical trials were found for WHO-recommended treatment of drug-resistant TB treatment where at least 20% of the cohort was coinfected with HIV. Nearly all patients (83%) experience ADR during DR-TB treatment. While no significant association between ADR and HIV coinfection was found, further research is needed to determine whether concomitant antiretrovirals or immunosuppression increases the risks for HIV-infected patients.

PHARMACOVIGILANCE: AN INEVITABLE PATH TOWARDS DRUG SAFETY IN INDIA

Thalidomide disaster is one of the overturn jolt in the field of allopathic medicine that attracted the attention of practitioner all over the world towards adverse effects of drugs, then only the actual concept of monitoring of adverse drug reactions came into limelight. Pharmacovigilance is t he science and activities relating to the detectio n, assessment, understanding and prevention of adverse effects or any other p ossible drug - related problems . Pharmacovigilance not only allopathic drugs; but also include herbals, traditional medicines, blood products (Haemovigilance) , biological (biovigila nce), medical devices (materiovigilance) & vaccines. United Kingdom firstly introduced the yellow card for adverse drug reaction reporting. In India pharmacovigilan ce came into existence in 2010. Indian pharmacopoeia commission (IPC) is the national coordi nating centre for pharmacovigilance program of India, responsible for collection, assessment of reported ADRs from the various adverse drug rea ction monito ring centers & pharmaceutical co mpanies, also consulting central drug standard control organization (CDSCO) in generation of signal. IPC is also collaborating with World health organization (WHO) drug safety program. Main source of data collection of ADRs is spontaneous reporting method & mainly from healthcare professionals. For drugs, IPC - suspected ADRs reporting form for healthcare Professionals is used for reporting ADRs by doctors. IPC - has currently availed the ADRs reporting form for patie nt in english & local languages . National institute of b iologicals - has availed the form for Haemovigilance . Pharm acovigilance target to wards signal detection , creating warning, restricting drug use, sometimes withdrawal of drug from market & finally decreasing mortality & risk of ADRs in patients.

Demand for genetic test for reducing risk of serious ADRs

Demand for genetic test for reducing risk of serious ADRs

Demand for genetic test for reducing risk of serious ADRs

Demand for genetic test for reducing risk of serious ADRs

More than skin deep. Ten year follow-up of delayed cutaneous adverse drug reactions (CADR).

To determine the gaps in practice regarding appropriate ADR documentation and risk communication for patients diagnosed with severe cutaneous adverse drug reactions (CADR). This was a retrospective observational cohort study conducted using hospital coding and databases to identify inpatients diagnosed with CADR from January 2004 to August 2014. Hospital discharge summaries, ADR reports and pharmacy dispensing records were reviewed for ADR documentation. Patients still living in Australia and who did not opt out of being contacted were invited to be surveyed by telephone to determine their understanding of recommendations, re-exposure rates and long-term effects. Of 85 patients identified, median age was 59 (IQR 44-72) years and 47.1% were male. The most common diagnosis was TENS (49.4%). Ten patients (11.8%) died as inpatients. Of the 81 patients with a drug-related causality, 47 (58%) had appropriate documentation in all three required medical record platforms. Of the 56 eligible patients, 38 (67.9%) were surveyed; 13% had no information provided upon discharge and 26.3% patients had a mismatch in knowledge of implicated medications. No surveyed patient had a relapse of CADR, but 23.7% had a subsequent unrelated allergic reaction. Thirteen patients (34.2%) reported long-term effects. We found gaps in the accuracy of ADR documentation and communication of risk at discharge, which indicated risks to patient safety. Electronic systems are being developed to improve documentation. Written information about CADR is being provided at discharge to improve patient understanding and knowledge.

ADR risk increases with increased off-label use

ADR risk increases with increased off-label use

Pharmacovigilance in Pediatric Age: The Role of Family Pediatricians- Medicines for Children Research Network (FP-MCRN)

The conduct of pharmacovigilance for paediatric use medicines requires special attention. Childhood diseases and disorders may be qualitatively and quantitatively different from their adult equivalents. Lack of clinical studies in the paediatric population leads as a consequence to drug prescriptions on an unlicensed or ‘off-label’ basis, because they have not been adequately tested and/or formulated and authorised for use in appropriate paediatric age groups. Spontaneously reported suspected adverse drug reactions remain the most important source in order to promote reasonable warning signals. Pre-marketing trials are able to provide information about the benefits of drugs but do not manage to establish a safety profile. Post Authorization Safety Studies (PASS), give much more reliable estimates of the risk of ADRs than those resulting from spontaneous reports. An improvement Family Paediatricians (FP) Pharmacovigilance training and continuous family information on the correct use of paediatric drugs may generate a better compliance of ADRs understanding. In this context, Family Paediatricians -Medicines for Children Research Network (FP-MCRN), ENPREMA and ENCEPP member, established with the aim of developing competence, infrastructure and education for paediatric clinical trials, plays a crucial role in paediatric Pharmacovigilance (PV), through an improvement of PV paediatricians training, a correct research methodology and very strong relationship with the families.

The efficacy of bisphosphonates in preventing aromatase inhibitor induced bone loss for postmenopausal women with early breast cancer: a systematic review and meta-analysis.

Objectives. We aim to determine the efficacy of bisphosphonates in preventing aromatase inhibitor induced bone loss (AIBL) in postmenopausal women with early breast cancer. The secondary objective was to determine the safety of bisphosphonates. Materials and Methods. We searched electronic databases in a time period of 1995 January to 2013 June. Random effects meta-analytical models were used; between study heterogeneity and publication bias was assessed. Results. A total of six eligible studies reported the BMD T score of LS at 12 months and from that 3 trials of Zoledronic acid compared the change in BMD in immediate ZOL versus delayed ZOL done with subgroups like patients with normal BMD at baseline (OR = 5.402, 95% CI = 1.329–21.959, P value = 0.018) and osteopenic BMD at baseline (OR = 4.008, 95% CI = 2.249–7.143, P value = 0.0002). Both had a significant decrease in BMD that favoured the delayed ZOL; 3 trials of risedronate and ibandronate also had a significant decrease in BMD in AIs alone group. Immediate ZOL versus delayed ZOL also showed increased risk of getting an ADR in immediate group. Conclusion. Third generation bisphosphonates has an effect on BMD of patients who are on treatment of AIs in breast cancer. Furthermore, the patients treated with immediate ZOL had a significantly high risk of musculoskeletal ADR's than patients with delayed ZOL.

PCV116 - Persistence with Medications: A Discrete Choice Experiment of Preferences Among Hypertensive Patients

To examine patients’ stated preferences for persisting with medications using a discrete choice experiment (DCE) and to explore the relationship with clinical, demographic and psycho-social variables. A 4-attribute DCE (mild side-effects, potentially life-threatening but rare side-effects, dose frequency, treatment benefits) with 3-levels identified from literature and expert opinion was developed using a fractional factorial design. Scenarios were folded into nine forced binary choices: Which medicine would you be most likely to continue taking? The survey was translated, piloted and approved for eleven European countries. Target sample was 100≤n≤323 patients prescribed anti-hypertensives per country, recruited by posters in community pharmacies or general practices. Results were analysed in STATA using a random effects logit model. A total of 2856 patients from Austria (n=323), Belgium (n=180), England (n=323), Germany (n=265), Greece (n=289), Hungary (n=323), The Netherlands (n=237), Poland (n=323) and Wales (n=323) completed the online questionnaire. All four attributes influenced persistence with treatment (p<0.01). Patients were willing to forego chance of improvements in treatment benefits (%) in order to improve other attributes: -36.10% (95% CI: -41.24 to -32.94) for a very rare risk of life-threatening side-effects; -18.66% (95% CI: -21.51 to -16.67) for once daily dose frequency; -0.74% (95% CI: -0.85 to -0.67) to reduce the risk of mild ADR by 1%. Likelihood ratio tests showed that models controlling for clinical, demographic and psycho-social variables were significantly different from the base-case. There was limited evidence that self-reported adherence influenced stated preferences to persist. Patients were willing to trade potential benefits, harms, and convenience in responding that they would persist with treatment. Clinical, demographic and psycho-social factors influence the extent of the trade-offs between these attributes. Persistence may therefore be enhanced directly, through selection of medicines meeting preferred levels of attributes, or indirectly through targeting modifiable psycho-social factors that affect trade-off choices.

Off-label drug use in children increases risk of ADRs

Off-label drug use in children increases risk of ADRs

PP027—Drug-induced liver injury detected through a pharmacovigilance program based in laboratory signals

e26 Volume 35 Number 8S Results: The pharmacovigilance program involved 1 general hospital (Ass.2 ‘Isontina’, Gorizia-Italy), 12 pharmacies, and 24 GPs. From March 2012 to March 2013, Medigenia enrolled 2074 patients (52.4% women; mean age, 69 [8]).The system totally administered 62,499 drugs (68.2% prescriptions, 28.4% OTC, and 3.4% herbs), and 3028 were the DDIs identified among them. GPs received 2738 alerts for ADR risk (48% moderate risk, 23.2% high risk): treatment was changed 871 times (31.8%).The most frequent alert among high risk connected with hemorrhage (87.6%), involving primarily acetyl-salicylic acid and warfarin. Moderate risk concerned mainly neurologic sequels (38.2%) and involved in particular antineoplastic agents and phenytoin. Conclusion: People taking drugs are not always aware of the health risk they are going toward after a multidrug therapy or simply taking a medicine without asking GP, a trend that is increasing in the last years. Medigenia prevents ADR and their health sequels using a cloud-based approach for pharmacovigilance. Disclosure of Interest: None declared.

10 The Stem Cell-Targeting Drug Salinomycin Inhibits Proliferation of Normal, Benign Hyperplastic, and Transformed Interstitial Cells of Cajal and Their Stem Cells (ICC-SC) by Increasing the Expression of Cell Cycle Restriction Checkpoint Regulators

the index colonoscopy to the first of the following: 10 years follow-up; performance of another colonoscopy without CRC; termination of membership; diagnosis of CRC; or January 31, 2011. CRCs occurring within 6 months after the index colonoscopy were excluded. Analyses used multi-level Cox proportional hazards models with clustering on physician. Potential predictors of subsequent CRC risk included physician ADR, exam type, and patient sex, age, race/ethnicity, family history of CRC, and Charlson comorbidity score. Hazard ratios (HR) for subsequent CRC risk were calculated separately by patient sex and both sexes combined, and by distal and proximal CRC location (both sexes combined). Results: We identified 316,334 colonoscopy exams and 716 subsequent post-colonoscopy CRC cases for the analyses. Patients (both sexes combined) whose colonoscopies were performed by endoscopists with lower ADRs were more likely to be diagnosed with subsequent CRC than patients whose endoscopists had a higher ADR. The adjusted HRs (and CIs) for ADR quartiles of ,20.3%, 20.3%-25.2%, and 25.3%-32.0%, as compared to ≥32.1%, were 1.74 (1.36, 2.24), 1.52 (1.14, 2.04), and 1.31 (1.00, 1.73), respectively (Table). The relationships between ADR and subsequent CRC risk by proximal and distal location were similar (Table). Finally, the linear relationship between ADR and CRC risk did not vary by patient sex. Conclusions: Physician ADR is an independent predictor of subsequent CRC risk following a negative colonoscopy, the relationship does not vary by patient sex, and the relationships were similar for proximal and distal cancers. The use of ADR as a quality measure of colonoscopy’s ability to prevent subsequent cancers appears warranted; cancer risk increases linearly with decreasing physician ADR and there was no clear threshold above which there was no further improvement.