Number Of Adverse Drug Reactions Research Articles

Fresh Seed Supplementation of Syzygium Cumini Attenuated Oxidative Stress, Inflammation, Fibrosis, Iron Overload, Hepatic Dysfunction and Renal Injury in Acetaminophen Induced Rats

Nowadays, the drug induced organ damage has increased drastically. Similarly, number of Adverse Drug Reactions (ADR) is on the rise. Unwanted and harmful effects of a drug have been a good reason for early withdrawal of a good molecule from the market or clinical trial. In the present study, we have investigated the preventive role of Syzygium cumini against Acetaminophen induced organ damage. In this study, four different groups of rats were evaluated. Group A serves as a control group, Group B serves as control + Syzygium cumini group, Group C serves as disease group and Group D serves as disease + treatment group. Only two groups have been treated and exposed to an overdose of acetaminophen. However, liver and kidney markers like Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), Alanine Transaminase (ALT), Creatinine and Uric acid (UA) were measured respectively. Moreover, oxidative stress markers such as Malondialdehyde (MDA), Nitric Oxide (NO) and Advanced Oxidation Protein Product (AOPP) were found higher in acetaminophen overdose rats compared to control rats. Furthermore, antioxidant enzymes like Catalase (CAT), Superoxide Dismutase (SOD) and Linear Peptide Glutathione (GSH) were restored significantly by Syzygium cumini seed treatment. Finally, our study revealed that supplementation of 1% Syzygium cumini seed with food attenuated inflammatory cell infiltration, collagen secretion, extracellular matrix deposition and iron overload in both hepatic and kidney. We assume that the protection might be achieved due to having strong antioxidant properties of Syzygium cumini.

Evaluation of adverse drug reaction profile of antiretrovirals in HIV-positive patients in a tertiary care hospital

Background: Adverse drug reactions (ADRs) to antiretrovirals have been a matter of concern as they can affect patient compliance and treatment outcome. Hence, it is important to detect them early and institute appropriate treatment. Aims and Objective: To assess the prevalence, distribution, causality, severity, predictability and preventability of ADRs to antiretrovirals and to identify risk factors for their development in a tertiary care hospital in South India. Materials and Methods: This was a descriptive observational study. Data were collected from the case records of adult, treatment naive HIV-positive patients, newly initiated on antiretroviral drugs, January 2012 onward and closure of data set was on 31st December 2014. Results: A total of 238 cases met the inclusion criteria. Overall, 56 ADRs were noted. ADRs were observed in 39 males and 17 females. They were common in the age group 51-60 years. Anemia was the most common ADR followed by rash and hyperpigmentation. Most of the ADRs observed were of mild severity, requiring neither change in regimen nor any specific treatment. Zidovudine caused the highest number of ADRs, followed by nevirapine and stavudine. Most ADRs occurred within 6 months of starting antiretroviral therapy (ART). Causality relationship between drug and ADR was graded as “possible” according to WHO causality assessment scale. No statistically significant correlation of age, gender, weight, hemoglobin, CD4 count and the presence of opportunistic infections to the development of ADRs were noted. Conclusion: Regular monitoring, early detection of ADRs to antiretrovirals and their treatment is essential to optimize ART.

Treatments that generate higher number of adverse drug reactions and their symptoms

Objectives. Adverse drug reactions (ADRs) are an important cause of morbidity and mortality worldwide and generate high health costs. Therefore, the aims of this study were to determine the treatments which produce more ADRs in general population and the main symptoms they generate. Methods. An observational, cross-sectional study consisting in performing a self-rated questionnaire was carried out. 510 patients were asked about the treatments, illnesses and ADRs, they had suffered from. Results. 26.7% of patients had suffered from some ADR. Classifying patients according to the type of prescribed treatment and studying the number of ADR that they had, we obtained significant differences (p ≤ 0.05) for treatments against arthrosis, anemia and nervous disorders (anxiety, depression, insomnia). Moreover, determining absolute frequencies of these ADRs appearance in each treatment, higher frequencies were again for drugs against arthrosis (22.6% of patients treated for arthrosis suffered some ADR), anemia (14.28%), nerve disorders (13.44%) and also asthma (16%). Regarding the symptoms produced by ADRs, the most frequent were gastrointestinal (60% of patients who suffered an ADR, had gastrointestinal symptoms) and nervous alterations (dizziness, headache, sleep disturbances etc) (24.6%). Conclusion. Therapeutic groups which produce more commonly ADRs are those for arthrosis, anemia, nervous disorders and asthma. In addition, symptoms which are generated more frequently are gastrointestinal and nervous problems. This is in accordance with the usual side effects of mentioned treatments. Health professionals should be informed about it, so that they would be more alert about a possible emergence of an ADR in these treatments. They also could provide enough information to empower patients and thus, they probably could detect ADR events. This would facilitate ADR detection and would avoid serious consequences generated to both patients’ health and health economics.

Safety Profile of Nifurtimox and Treatment Interruption for Chronic Chagas Disease in Colombian Adults.

Nifurtimox (NFX) is one of the approved drugs used to treat Chagas disease. Safety profile studies and models on risk factors for treatment interruption in adults are scarce in Latin America. This study evaluated retrospectively the medical records of adult Chagas disease patients treated with NFX between 2007 and 2012 in Bogotá, Colombia. An accelerated failure time model was used, and associations were expressed as time ratio (TR). In total, 76 adult patients with NFX were included: 60 (79.0%) completed 60 days of treatment, 61 (80.3%) presented adverse drug reactions (ADRs), and 16 (21.0%) required treatment interruption. The predominant symptoms were epigastric pain (23.7%), nauseas (18.4%), sleep disturbances (18.4%), loss of appetite (17.1%), and temporary loss of memory (15.2%). ADRs were classified as mild (64.5%), moderate (30.4%), and severe (5.1%). Time of treatment was significantly longer when presenting ≤ 3 ADRs (TR: 1.78; 95% CI: 1.04–3.03), presence of non-severe ADRs (TR: 6.52; 95% CI: 3.24–13.1), doses of NFX ≤ 8 mg/kg/day (TR: 1.78; 95% CI: 0.90–3.49), and age < 48 years (TR: 1.57; 95% CI: 0.90–2.74). Treatment with NFX in adults caused a high frequency of ADRs, but most of the cases were mild and did not require treatment interruption. Severity and number of ADRs were the main predictors for treatment interruption.

Étude pilote permettant de calculer le ratio d’effets indésirables médicamenteux par 10 000 doses définies journalières et 10 000 jours de traitement d’anti-infectieux en 2012–2013

As part of our antimicrobials stewardship program, we were interested in the use of antimicrobials and prevalence of adverse drug reactions associated with the use of these drugs.The retrospective and descriptive study was conducted over a one year-period between April 1st 2012 and March 31st 2013 in a mother-child Hospital. We determined the ratio: number of adverse drug reactions over 10,000 defined daily dose or 10,000days of therapy. We identified the ratios higher than average for which the confidence interval did not cross the calculated average. The severity of the adverse drug reactions was codified using the Common Terminology Criteria for Adverse Events.We found 570 adverse drug reactions including 100 (17.5%) adverse drug reactions related to antimicrobials during the financial year 2012-2013. It represented 96 patients. Thus, five antimicrobials, for which the confidence interval does not cross the calculated average value, may be targeted in risk management because they have a higher ratio than average: piperacillin (290 [113-722]), valganciclovir (244 [43-1260]), ceftriaxone (114 [56-234]), acyclovir (76 [26-220]) and liposomal amphotericin B (72 [20-258]).In a mother-child university hospital, we calculated a ratios of 19 [15-23] and 13 [10-15], it allows us targeting some antimicrobials in our approach to prevention and management of adverse drug reactions.

English

The aging process is followed by an increase in the number of chronic diseases and, thus, the use of multiple medicines and prevalence of drug-related problems (DRP). This paper aims to identify the impacts of Pharmacotherapy follow-up (PF) in elderly with chronic non-communicable diseases while in polypharmacy using, in the public health service of Brazil. A prospective cohort study with 45 elderly of both sexes was done. Socioeconomic and pharmacotherapy data was collected at the first pharmaceutical appointment. According to the pharmacotherapeutic needs of each case were applied interventions for four appointments as blood pressure and blood glucose monitoring, schedule control medicine use and prescription changes by the letter to prescriber. Some variables as blood pressure, blood glucose, body weight, adverse drug reactions, negative outcomes associated with medication, drug-drug interactions and adherence were compared after 3, 6 and 12 months of follow-up during baseline in order to evaluate the impact of the study. Sample included elderly with a mean age of 71 years old, mainly low income and low education women. After 12 months of PF, pharmacotherapy adherence has shown an improvement (21.3 vs 52.4%), as well as a decrease in the number of adverse drug reactions (-1.61), drug-drug interactions (-1.17) and negative outcomes associated with medication (-2.49). &nbsp;Besides, there was better control of systolic blood pressure (-5.89 mmHg), body mass index (-2.01) and blood glucose (-12.51 mg/dl) besides plasmatic levels of lipoproteins, vitamin D and thyroid hormones. Results show evidence of PF importance as a strategy to improve adherence to pharmacological treatment, reduce drug-drug related problems and promote better quality of pharmacotherapy. Hence, better health for medication users. Key words: Pharmaceutical care, pharmaceutical service, patient adherence, pharmacist, drug therapy, aged, medication therapy management.

A Multicenter Evaluation of Off-Label Medication Use and Associated Adverse Drug Reactions in Adult Medical ICUs.

Prior research indicates that off-label use is common in the ICU; however, the safety of off-label use has not been assessed. The study objective was to determine the prevalence of adverse drug reactions associated with off-label use and evaluate off-label use as a risk factor for the development of adverse drug reactions in an adult ICU population. Multicenter, observational study : Medical ICUs at three academic medical centers. Adult patients (age ≥ 18 yr old) receiving medication therapy. All administered medications were evaluated for Food and Drug Administration-approved or off-label use. Patients were assessed daily for the development of an adverse drug reaction through active surveillance. Three adverse drug reaction assessment instruments were used to determine the probability of an adverse drug reaction resulting from drug therapy. Severity and harm of the adverse drug reaction were also assessed. Cox proportional hazard regression was used to identify a set of covariates that influenced the rate of adverse drug reactions. Overall, 1,654 patient-days (327 patients) and 16,391 medications were evaluated, with 43% of medications being used off-label. One hundred and sixteen adverse drug reactions were categorized dichotomously (Food and Drug Administration or off-label), with 56% and 44% being associated with Food and Drug Administration-approved and off-label use, respectively. The number of adverse drug reactions for medications administered and the number of harmful and severe adverse drug reactions did not differ for medications used for Food and Drug Administration-approved or off-label use (0.74% vs 0.67%; p = 0.336; 33 vs 31 events, p = 0.567; 24 vs 24 events, p = 0.276). Age, sex, number of high-risk medications, number of off-label medications, and severity of illness score were included in the Cox proportional hazard regression. It was found that the rate of adverse drug reactions increases by 8% for every one additional off-label medication (hazard ratio = 1.08; 95% CI, 1.018-1.154). Although adverse drug reactions do not occur more frequently with off-label use, adverse drug reaction risk increases with each additional off-label medication used.

Adverse drug reaction reports for cardiometabolic drugs from sub-Saharan Africa: a study in VigiBase.

Identifying key features in individual case safety reports (ICSR) of suspected adverse drug reactions (ADRs) with cardiometabolic drugs from sub-Saharan Africa (SSA) compared with reports from the rest of the world (RoW). Reports on suspected ADRs of cardiometabolic drugs (ATC: A10[antidiabetic], B01[antithrombotics] and C[cardiovascular]) were extracted from WHO Global database, VigiBase(®) (1992-2013). We used vigiPoint, a logarithmic odds ratios (log2 OR)-based method to study disproportional reporting between SSA and RoW. Case-defining features were considered relevant if the lower limit of the 99% CI>0.5. In SSA, 3773 (9%) of reported ADRs were for cardiometabolic drugs, in RoW for 18%. Of these, 79% originated from South Africa and 81% were received after 2007. Most reports were for drugs acting on the renin-angiotensin system (36% SSA & 14% RoW). Compared with RoW, reports were more often sent for patients 18-44years old (log2 OR 0.95 [99 CI 0.80; 1.09]) or with non-fatal outcome (log2 OR 1.16 [99 CI 1.10; 1.22]). Eight ADRs (cough, angioedema, lip swelling, face oedema, swollen tongue, throat irritation, drug ineffective and blood glucose abnormal) and seven drugs (enalapril, rosuvastatin, perindopril, vildagliptin, insulin glulisine, nifedipine and insulin lispro) were disproportionally more reported in SSA than in the RoW. 'In recent years, the number of adverse drug reactions (ADRs) reported in Sub-Saharan Africa (SSA) has sharply increased. The data showed the well-known population-based differential ADR profile of ACE inhibitors in the SSA population.'

Antiepileptic Drugs and Quality of Life in Patients with Epilepsy: A Tertiary Care Hospital-Based Study

ObjectivesThe present study evaluated patterns of the use of antiepileptic drugs (AEDs) and their impact on quality of life (QOL) in patients with epilepsy. MethodsIn this cross-sectional study, patients with epilepsy (age >18 years) receiving AEDs for at least 1 year were enrolled. Demographic, clinical, and treatment parameters were recorded. QOL was measured using the modified Quality of Life in Epilepsy Inventory-10 (QOLIE-10) questionnaire for epilepsy. ResultsOf 200 patients, 53.5% were males and 60% were younger than 30 years. Seizures were predominantly partial (58%) and of idiopathic origin (61%). Monotherapy to polytherapy ratio was 1:1, with 70% of the patients on one new AED. Clobazam (37%) was used most frequently followed by phenytoin (25.5%), levetiracetam (23%), oxcarbazepine (21.5%), and carbamazepine (21%). Patients on polytherapy experienced a significantly more number of adverse drug reactions than did those on monotherapy (P < 0.0001). The mean QOLIE-10 score was 74.58 ± 20.60. There was no significant difference in seizure frequency, number of adverse drug reactions, and QOLIE-10 score among patients receiving old and new AEDs. Multiple linear regression analysis identified increased seizure frequency (standardized β −0.157; P = 0.003), more number of AEDs (standardized β 0.107; P = 0.05) as well as adverse drug reactions (standardized β −0.692; P = 0.0001) as significant predictors of poor QOL. ConclusionsAppropriate tools for early detection, selection of rational and safer AED treatment options, and regular monitoring for adverse effects play a crucial role in achieving seizure freedom and optimal QOL in patients with epilepsy.

The pattern and risk factors associated with adverse drug reactions induced by Reteplase in patients with acute ST-elevation myocardial infarction: The first report from Iranian population.

Objective:Acute myocardial infarction (AMI) is one of the main leading causes of mortality and morbidity. Reteplase is a fibrin-specific thrombolytic which is used in the treatment of AMI. There is a limited number of studies reporting the postmarketing adverse drug reactions (ADRs) induced by reteplase. This study was aimed to examine the reteplase pattern of ADR and its associated risk factors in patients with acute ST-elevation myocardial infarction.Methods:A cross-sectional, prospective study in an 8-month period was done at the University affiliated referral cardiovascular center. The Naranjo probability scale and World Health Organization criteria for severity of ADRs were used for assessing the ADRs. The linear regression and logistic regression tests were used to evaluate the correlation between ADRs and risk factors.Findings:The all 20 patients who received reteplase during the study period were entered. The majority of patients (n = 17) experienced at least one ADR. The results showed that the incidence of ADRs was mainly associated with gender and age, and the number of ADRs was associated with the history of diabetes and taking anti-diabetic agents. The gender was the main predictor in the occurrence of ADRs (odds ratio: 32, 95% confidence interval: 1.38–737.45; P = 0.030).Conclusion:The results showed that gender, age, diabetes mellitus, and using of anti-diabetes medications are the risk factors associated with the incidence of ADRs by reteplase.

Levetiracetam (Keppra) efficacy and safety in the prevention of early-onset seizures following traumatic brain injuries in pediatric patients

AbstractIntroductionApproximately half a million emergency department visits for traumatic brain injury (TBI) by children and adolescents occur each year. One of the complications of TBI is early-onset seizure. Current guidelines recommend the use of phenytoin for prevention of seizures following a TBI; however, several drug interactions and adverse reactions are associated with its use. Despite studies demonstrating efficacy of levetiracetam in adult patients, the efficacy and safety of levetiracetam in children with TBI is unknown. The purpose of this study was to determine the efficacy and safety of levetiracetam for the prevention of early-onset seizures in pediatric patients following TBI.MethodsA retrospective evaluation was conducted, which included children, ages 0 to 17 years, admitted secondary to a nonpenetrating TBI and who received levetiracetam for seizure prophylaxis for up to 7 days. The primary outcome was the number of children who had a seizure within the first 7 days following a TBI, and secondary outcomes included the number of adverse drug reactions.ResultsA total of 89 pediatrics patients with nonpenetrating TBI were identified and included in the study. Forty-seven patients received a mean dose of 10 mg/kg (SD ± 4.22) of levetiracetam twice a day, and 42 patients received 500 mg 2 times per day (based on adult dosing). Seizure activity was observed in only two patients (2.2%) within the first 7 days following TBI. A total of 13 patients (14.6%) experienced anemia, agitation, and elevation of liver enzymes during levetiracetam therapy.DiscussionThe study suggests that levetiracetam appears to be an effective and safe agent for early-onset seizure prophylaxis in pediatric patients with TBI as indicated by the low number of patients with seizures. The reported adverse reactions may have resulted from the trauma rather than the use of levetiracetam.

Adverse drug reaction monitoring on antiretroviral therapy in human immunodeficiency virus patients in a tertiary care hospital

Background: The aim of current study was to assess the pattern of adverse drug reactions (ADRs) in patients receiving antiretroviral (ARV) therapy. Methods: A prospective, observational study was carried out for duration of 15 months. Clinical and treatment data were collected from patients, who underwent ARV therapy during the study period. CDSCO forms were used to record the ADRs. Causality, severity and preventability were assessed by suitable scales. Result: Out of 216 patients 165 (76%) patients develop ADRs. Total of 274 ADRs were noted among 165 patients (1.66 ADR/patient). Out of them 100 (60.60%) were males and 65 (39.39%) were females. The most common ADR was gastrointestinal disorders (83, 30.29%). The most numbers of ADRs were observed in ZLN (Zidovudine + Lamivudine + Nevirapine) regimen (54%) followed by SLN (Stavudine + Lamivudine + Nevirapine) regimen (26%). According to WHO causality assessment scale most ADRs were possible (236, 86.13%). Hartwig and Siegel severity scale show 243 (88.69%) ADRs were moderate. Schumock and Thornton scale show all, ADRs were “not preventable.” Conclusion: Early detection of drug toxicity helps to treat the patient and modify the drug regimen to minimize toxic effects.

Penicillin to prevent recurrent leg cellulitis: a critical appraisal.

Thomas et al. compared the effectiveness of prophylactic low‐dose penicillin vs. placebo in patients with recurrent cellulitis for preventing the disease. Participants of this double‐blind randomized controlled trial were recruited at 28 hospitals in the U.K. and Ireland between July 2006 and January 2010. Patients with two or more episodes of cellulitis of the leg were randomized to receive low‐dose oral penicillin (250 mg twice daily) or placebo over 12 months with a follow‐up period of up to 3 years. The primary outcome was the time to a first recurrence. Secondary outcome measures were the proportion of participants with a repeat episode of cellulitis during the prophylaxis phase and during the follow‐up phase, the number of repeat episodes of cellulitis, the proportion of participants with new oedema or ulceration during the prophylaxis phase and during the follow‐up phase, the number of nights in hospital for cellulitis, the number of adverse drug reactions or adverse events of interest (death, nausea, diarrhoea, thrush, rash, severe skin reactions, sepsis and renal failure), cost–effectiveness and predictors of response. Of the 533 patients screened, 274 were eligible and included in the trial (136 were assigned to the penicillin group and 138 to the placebo group). The median time to a first recurrence of cellulitis was 626 days in the penicillin group and 532 days in the placebo group. During the 12 months of treatment 30 (22%) of 136 patients in the penicillin group had a recurrence compared with 51 (37%) in the placebo group [hazard ratio 0·55, 95% confidence interval (CI) 0·35–0·86, P = 0·01; number needed to treat 7, 95% CI 4–9]. After the 12‐month treatment period, during the follow‐up there was no difference in the rate of first recurrence (27% in both groups). There were fewer repeat episodes in the penicillin group than in the placebo group during the treatment period (76 vs. 122, P = 0·03) and no difference during subsequent follow‐up (43 vs. 42). There was no statistically significant difference between the groups in the number of participants with an adverse event (37 in the penicillin group vs. 48 in the placebo group, P = 0·50). Thomas et al. concluded that low‐dose penicillin was effective in preventing recurrent cellulitis in people with recurrent disease during prophylactic treatment, but that the effect reduced progressively after the discontinuation of penicillin.

Which adverse effects influence the dropout rate in selective serotonin reuptake inhibitor (SSRI) treatment? Results for 50,824 patients.

Background: Nowadays, selective serotonin reuptake inhibitors (SSRIs) are the most frequently prescribed antidepressants due to their superior clinical efficacy, effectiveness, tolerability, and safety as compared to tricyclic antidepressants or monoamino oxidase inhibitors. However, despite these advantages SSRIs are still associated with a number of adverse drug reactions, especially in the early stages of treatment, which may lead to premature discontinuation of therapy in some cases. The aim of the present study was to assess the most common adverse drug reactions of SSRIs as well as their impact on dropout rate in a large study population.Patients and methods: Data for 50,824 patients treated for major depressive disorder with SSRIs for the first time was accessed via the Disease Analyzer database (IMS Health, Germany), providing information on SSRI adverse drug reactions and their influence on premature treatment discontinuation calculated by regression analysis. The presence of certain co-morbidities was also registered. Results: The mean age was 54.5 ± 19 years, two-thirds of the study population being female. The adverse effects mentioned most frequently were: “discomfort” of the digestive system (10%), sleep disorders (8.6%), and heart rhythm disorders (4%); however, these were of tolerable severity as they did not significantly influence the dropout rate. Contrary to that, somnolence and younger age (≤50 years) in particular increased the chance of premature treatment discontinuation, while patients suffering from cardiovascular risk factors or osteoporosis tended to adhere to the therapy.Conclusions: Overall, there is high tolerability for early SSRI treatment, whereas the occurrence of somnolence leads to discontinuation.

Use of administrative hospital database to identify adverse drug reactions in a Pediatric University Hospital

The aim of the study was to detect adverse drug reactions (ADRs) in pediatric inpatients using the medical administrative database "Programme de Médicalisation des Systèmes d'Information" (PMSI) and to compare these cases ADRs with those spontaneously reported to a regional PharmacoVigilance (PV) Centre. The study was conducted from January 2008 to December 2011 in the Children University Hospital of Toulouse (Midi-Pyrénées, South-west France). From PMSI database, all discharge summaries including selected ICD-10 codes (10th International Classification of Diseases) were analyzed. All ADRs spontaneously reported by the Children Hospital of Toulouse and registered in the French PV Database (FPVDB) were included. The capture-recapture method was applied to estimate the incidence of ADRs. During the study period, we identified 60 reports from the PMSI database and 200 from the FPVDB. The rate of "serious" ADRs was higher in PMSI reports (74.6% vs 38.9%, p < 0.0001). The most frequent ADRs reported were musculoskeletal (12.4%) and central (11.3%) ADRs in PMSI database versus cutaneous (22.4%) and general (17.5%) ADRs in FPVDB. The most frequently suspected drugs were antineoplastic drugs (31.1%) in PMSI database versus anti-infectives (38.2%) in FPVDB. The estimated number of ADRs was 717 [95% confidence interval (CI) 513, 921], and the incidence of ADRs among admissions was 0.6% (95% CI 0.4, 0.8). Use of PMSI database improves from around 30% detection of ADRs in children. In comparison with classical pharmacovigilance database, it also allows to detect different ADRs and drugs, thus enhancing safe medicine use for pediatric patients.

Evaluation of a Once-Daily Vancomycin Regimen in an Outpatient Leukemia/Bone Marrow Transplant Clinic (OD-VANCO Study).

The Leukemia/Bone Marrow Transplant Program of British Columbia manages patients with high-risk febrile neutropenia and those with non-neutropenic immunocompromised states in an outpatient clinic setting. Because the program treats outpatients only, once-daily administration of IV antibiotics is desirable. A high-dose, once-daily vancomycin nomogram was developed and implemented as part of the antibiotic treatment regimen. To determine if therapeutic vancomycin trough levels could be achieved with a high-dose, once-daily regimen in this outpatient setting. A prospective, single-centre, observational cohort study was conducted over a 7-month period. Outpatients in the Leukemia/Bone Marrow Transplant Program were started on IV vancomycin with the high-dose, once-daily vancomycin nomogram, and outcomes were assessed. Of 48 outpatients treated over the 7-month period, 10 (21%) had therapeutic vancomycin trough concentrations (i.e., greater than 10 mg/L). Thirty-five (90%) of the 39 patients with suspected clinical infection experienced clinical cure, and 6 (67%) of the 9 patients with documented microbiological infection experienced microbiological cure. Thirty (62%) of the 48 patients experienced symptoms of "red man syndrome", and 7 (15%) experienced some degree of nephrotoxicity. Two of 3 patients with laboratory-reported minimum inhibitory concentration (MIC) for identified pathogens had a calculated area under the curve to MIC ratio greater than or equal to 400. The high-dose, once-daily vancomycin nomogram was effective in attaining trough levels greater than 10 mg/L in only 21% of patients in this study. A substantial number of adverse drug reactions were observed. Given these results, high-dose, once-daily vancomycin is no longer recommended for outpatient therapy.

Assessment of outlook of adverse drug reaction monitoring and reporting and its importance among the experienced doctors, interns and the nursing staff in a tertiary care center (kims)

Adverse drug reactions (ADR) are frequently observed during the course of therapy in a substantial number of patients. Despite having an operational pharmacovigilance programme in India still we have seen fewer number of ADRs reported than actually encountered. This points towards a definite lacunae regarding the knowledge and interest among the healthcare providers in India regarding ADR monitoring and reporting. ADR reporting helps us to identify safety issues associated with any medicinal products that was till now not known , that in turn helps in formulating proper and flawless national drug policy. This study was aimed to provide quality healthcare to the people of the country, to generate awareness to the healthcare providers and to make them understand the importance of pharmacovigilance centre in the tertiary care hospital. A cross sectional study was done at Kalinga Institute of Medical Sciences, Bhubaneswar. A predetermined questionnaire comprising 30 questions were formed to assess knowledge, attitude, and interest of responders. Total 150 healthcare personnel have been taken into account. They were sub-divided among 3 groups i.e. experienced doctors, nursing staffs and medical interns. Each group comprises of 50 personnel. Most of the questions in questionnaire were of binomial in type (single response / yes no). Scoring based on attempt and number of correct responses. Likert scale used to describe the obtained score qualitatively. After analysing whole sets of data with appropriate statistical methods it was observed that for proper attitude and interest each group requires separate approach. Each group needs to be individualised and requires categorical action. More continuous medical education and workshops are required for this. Adverse drug reaction reporting should be made voluntary and all healthcare providers should come together for this cause.

Variation in the CYP2D6 genotype is not associated with carvedilol dose changes in patients with heart failure

Carvedilol is the standard of care for heart failure (HF) patients. Carvedilol is partially metabolized by the highly polymorphic enzyme, CYP2D6. To reach an effective dose while avoiding adverse drug reactions (ADRs), testing of CYP2D6 genotype prior to carvedilol initiation may be considered. The objectives of this study were to determine CYP2D6 metabolic genotypes in an Israeli cohort of HF patients and to investigate the relationship between genotype, carvedilol dose and number of ADRs to determine the importance of CYP2D6 genotyping prior to treatment initiation. Ninety-three patients with HF on carvedilol were CYP2D6 genotyped and classified as poor (PM), intermediate (IM), extensive (EM) or ultrarapid (UM) metabolizers. Carvedilol dose and ADRs were calculated and correlated with genotype using linear regression statistic analysis. The distribution of the CYP2D6 phenotype in the Israeli population with HF is similar to the European general population. There were no significant differences of carvedilol dose and number of ADRs among genotype groups. Genotype group affiliation and number of adverse drug reactions were not predictive of carvedilol dose changes. Genotype group affiliation and number of adverse drug reactions were not predictive of carvedilol dose during therapy for patients with HF. The Israeli CYP2D6 phenotype distribution in HF patients was consistent with the frequency in the general European population.

Apport du logiciel Nadis® dans la collecte des effets indésirables des antirétroviraux : expérience en Midi-Pyrénées

To study the value of the module of pharmacovigilance in Nadis® to improve the antiretroviral (ARV) drugs-induced adverse drug reactions (ADRs) reporting. We collected the ADRs reported for 17 months from November 2010 until April 2012. Following data were recorded: characteristics of patients, ADRs, ARV drugs. The number of ADRs was compared to those collected in the same period (17 months) before use of Nadis®. The 119 ADRs reported (an increase of 183%) for 109 patients ADRs were mainly gastrointestinal (21.8%) followed by renal (20.2%), neuro-psychiatric (16.8%), hepatic (13.5%), cutaneous (8.4%), metabolic (6.7%) and others (12.6%). The repartition of ARV drugs was: nucleoside (31.8%), nucleotide (13.6%) reverse transcriptase inhibitors respectively, non-nucleoside reverse transcriptase inhibitors (13.1%), protease inhibitors (36.4%), and integrase inhibitors (5.1%). Our results show the improvement of ARV-induced ADRs reporting by Nadis® which could be used to reduce the rate of under-reporting in patients exposed to these drugs.

Urinary Biomarkers of Trimethoprim Bioactivation in Vivo Following Therapeutic Dosing in Children

The antimicrobial trimethoprim-sulfamethoxazole (TMP-SMX) is widely used for the treatment of skin and soft-tissue infections in the outpatient setting. Despite its therapeutic benefits, TMP-SMX has been associated with a number of adverse drug reactions, which have been primarily attributed to the formation of reactive metabolites from SMX. Recently, in vitro experiments have demonstrated that TMP may form reactive intermediates as well. However, evidence of TMP bioactivation in patients has not yet been demonstrated. In this study, we performed in vitro trapping experiments with N-acetyl-l-cysteine (NAC) to determine stable markers of reactive TMP intermediates, focusing on eight potential markers (NAC-TMP adducts), some of which were previously identified in vitro. We developed a specific and sensitive assay involving liquid chromatography followed by tandem mass spectrometry for measurement of these adducts in human liver microsomal samples and expanded the methodology toward the detection of these analytes in human urine. Urine samples from four patients receiving TMP-SMX treatment were analyzed, and all samples demonstrated the presence of six NAC-TMP adducts, which were also detected in vitro. These adducts are consistent with the formation of imino-quinone-methide and para-quinone-methide reactive intermediates in vivo. As a result, the TMP component of TMP-SMX should be considered as well when evaluating adverse drug reactions to TMP-SMX.