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Adverse Drug Reactions (adverse + drug_reaction)
Kinds of Adverse Drug Reactions Selected AbstractsNew guideline for tramadol usage following adverse drug reactions reported to the Iranian pharmacovigilance center,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 2 2007K. Gholami Pharm D Abstract Background Tramadol was introduced as injection and oral form to Iranian Pharmaceutical Market in 2002. Shortly after, the injection form of the drug was observed at the top of suspected drug list of Adverse Drug Reactions (ADRs) received monthly by Iranian Pharmacovigilance Center (IPC). Objectives To detect, assess and report total number of Tramadol-induced ADRs received by IPC. To assess the frequency of reported Tramadol-induced ADRs before and after interventions. To design a guideline for prevention of probable ADRs due to Tramadol injection. Methods A descriptive study was conducted on spontaneous reporting received by IPC from April 2002 to February 2005. All ADRs suspected to be induced by Tramadol registered in the database during mentioned period were analysed. To assess the effect of different interventions based on Spontaneous Reporting System, the trend of reporting frequency of Tramadol-induced ADRs was evaluated before and after interventions. Results There were 337 cases of Tramadol-induced ADRs describing 939 reactions, reported to IPC during the study period. Although causal relationship had not been established, three cases of deaths appeared among the reports. The severity of reactions led to implementation of limitations on injectable Tramadol distribution to community pharmacies and the restriction of its use to hospitals only. Since most adverse reactions were dose-dependent, the drug potency of injectable Tramadol available in the country changed from 100,mg to 50,mg. The assessment of ADR reports received by IPC showed that the frequency of adverse reactions registered in the centre was reduced considerably following these interventions. Conclusion Designing a detailed programme by Pharmacovigilance Centres and closely monitoring of newly marketed pharmaceutical products is highly recommended. Copyright © 2006 John Wiley & Sons, Ltd. [source] Relationship between Serum Acetaminophen Concentration and N -Acetylcysteine-Induced Adverse Drug ReactionsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 3 2010Sa'ed H. Zyoud However, during the infusion of the loading dose, different types of adverse drug reactions (ADR) may occur. The objective of this study was to investigate the relation between the incidence of different types of ADR and serum acetaminophen concentration in patients presenting to the hospital with acetaminophen overdose. This is a retrospective study of patients admitted to the hospital for acute acetaminophen overdose over a period of 5 years (1 January 2004 to 31 December 2008). Parametric and non-parametric tests were used to test differences between groups depending on the normality of the data. SPSS 15 was used for data analysis. Of 305 patients with acetaminophen overdose, 146 (47.9%) were treated with intravenous N -acetylcysteine and 139 (45.6%) were included in this study. Different types of ADR were observed in 94 (67.6%) patients. Low serum acetaminophen concentrations were significantly associated with cutaneous anaphylactoid reactions but not other types of ADR. Low serum acetaminophen concentration was significantly associated with flushing (p < 0.001), rash (p < 0.001) and pruritus (p < 0.001). However, there were no significant differences in serum acetaminophen concentrations between patients with and without the following ADR: gastrointestinal reactions (p = 0.77), respiratory reactions (p = 0.96), central nervous reactions (p = 0.82) and cardiovascular reactions (p = 0.37). In conclusion, low serum acetaminophen concentrations were associated with higher cutaneous anaphylactoid reactions. Such high serum acetaminophen concentrations may be protective against N -acetylcysteine-induced cutaneous ADR. [source] Glutathione-S-transferase genotypes and the adverse effects of azathioprine in young patients with inflammatory bowel diseaseINFLAMMATORY BOWEL DISEASES, Issue 1 2007Gabriele Stocco PhD Abstract Background: Adverse drug reactions to azathioprine, the prodrug of 6-mercaptopurine, occur in 15%,38% of patients and the majority are not explained by thiopurine-S-methyltransferase (TPMT) deficiency. Azathioprine is known to induce glutathione depletion and consumption of glutathione is greater in cells with high glutathione-S-transferase (GST) activity compared with those with low activity; moreover, some reports indicate that GST might play a direct role in the reaction of glutathione with azathioprine. The association between polymorphisms of GST-M1, GST-P1, GST-T1, and TPMT genes and the adverse effects of azathioprine was therefore investigated. Methods: Seventy patients with inflammatory bowel disease (IBD), treated with azathioprine, were enrolled and clinical data were retrospectively determined. TPMT and GST genotyping were performed by polymerase chain reaction (PCR) assays on DNA extracted from blood samples. Results: Fifteen patients developed adverse effects (21.4%); there was a significant underrepresentation of the GST-M1 null genotype among patients developing adverse drug reactions to azathioprine (odds ratio [OR] = 0.18, 95% confidence interval [CI] = 0.037,0.72, P = 0.0072) compared with patients who did not develop adverse effects. Patients heterozygous for TPMT mutations presented a marginally significant increased probability of developing adverse effects (OR = 6.38, 95% CI = 0.66,84.1, P = 0.062). Moreover, among the 55 patients who did not develop adverse effects, there was a significant underrepresentation of the GST-M1 null genotype among patients who displayed lymphopenia as compared with those that did not display this effect of azathioprine (OR = 0.15, 95% CI = 0.013,1.08, P = 0.032). Conclusion: Patients with IBD with a wildtype GST-M1 genotype present increased probability of developing adverse effects and increased incidence of lymphopenia during azathioprine treatment. (Inflamm Bowel Dis 2007;13:57,64) [source] Adverse drug reactions to biologicsJOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 6 2010Kathrin Scherer Summary The use of biologics has rapidly expanded since the introduction of the first diagnostic antibodies; they are now widely employed in oncology, autoimmune disorders, inflammatory diseases and transplantation medicine. Their widespread use has resulted in an increase in adverse drug reactions. Adverse effects result from both direct pharmacological actions and immunological actions, as well as through induction of a specific immune response. The nomenclature, particularly of the monoclonal antibodies, identifies the target structure and organ as well as the species of origin, which then helps predict their effects and antigenic properties. Depending on the extent of foreign protein, anti-allotypic or anti-idiotypic antibodies with or without neutralizing properties may be induced. Adverse drug reactions from biologics often depend on the target and may be explained by activation or inhibition of particular cytokine pathways. Adverse drug reactions are classified by their pathomechanism, which enhances understanding of the pathogenesis and facilitates both allergologic diagnostic measures and planning of premedication in future treatments. This review emphasizes immunostimulatory and hypersensitivity reactions. [source] Administration of enoxaparin by continuous infusion in a naturalistic setting: analysis of renal function and safety,JOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 3 2005S. L. Kane-Gill Pharm D MSc Summary Study objective:, To describe the clinical use and safety of continuous infusion (CI) enoxaparin in a naturalistic setting and to evaluate the influence of renal function on enoxaparin elimination. Design:, Retrospective medical record review. Setting:, 1000-bed tertiary care teaching centre. Patients:, Hospitalized patients that received enoxaparin by CI during a 2-year period. Interventions:, None. Measurements:, Specific details of dosage and monitoring were collected. Adverse drug reactions (ADR) were recorded. Creatinine clearance (CrCl) was calculated using Cockroft and Gault and Brater equations. A population pharmacokinetic analysis was performed using the non-linear mixed effect model (NONMEM). For patients located in the intensive care unit (ICU) and ward, POSTHOC pharmacokinetic parameter estimates were evaluated using the Wilcoxon rank-sum. Pearson correlation coefficient was calculated to determine the association between renal function and anti-Xa clearance. Main results:, Sixty-seven patients received enoxaparin by CI of which 61·2% were in the ward and 38·8% in the ICU. The average initial rate and duration of infusion were 5·2 mg/h and 5·6 days, respectively. The number of anti-Xa concentration measurements averaged five per patient. Nine patients experienced an ADR. The most frequent ADR was gastrointestinal bleeding (n = 4). Among the 67 patients, 48 had available anti-Xa concentrations and were included in the NONMEM model. The anti-Xa CL and volume of distribution for ICU and ward patients averaged 0·64 ± 0·34 L/h, 10·6 ± 1·55 L and 1·01 ± 0·39 L/h, 9·08 ± 1·17 L, respectively. CrCl was not a significant covariate when included in the NONMEM model, and the association between CrCl and anti-Xa clearance was not significant (R2 = 0·0005; P = 0·8916). Conclusions:, This study is the first to report the use and safety of prolonged CI enoxaparin. Pharmacokinetic parameters of enoxaparin differ in ICU vs. ward patients. Overall, we found the safety of CI to be comparable to subcutaneous administration. Also, we found no effect of renal function on enoxaparin elimination. [source] Adverse drug reactions induced by cardiovascular drugs in cardiovascular care unit patients,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 9 2010Niayesh Mohebbi Pharm D Abstract Purpose To detect the type, rate, seriousness, and preventability of adverse drug reactions (ADRs) attributable to cardiovascular drugs in cardiovascular care unit; and to determine the relationship between patient factors and detected ADRs. Methods Patients admitted to cardiovascular care units in Tehran Heart Center over an eight month period who received at least one cardiovascular drug were eligible to enter the study. ADRs were recorded based on information collected by interviewing patients, reviewing patients' charts, laboratory test monitoring, and confirmation by physicians. The World Health Organization definition for ADR, its seriousness and casualty criteria, was used to evaluate the reactions. The preventability was estimated based on Schumock and Thornton questioning. The relationship between possible risk factors and ADRs occurrence were assessed by statistical analysis. Results During the study period, 677 patients entered the study. A total number of 189 ADRs were registered of which 22.2% were serious. The highest ADR rates were observed with Streptokinase (59.3%). The rate of preventable ADRs was 6.9%. Multivariate logistic regression analysis showed that patients with lower weight (OR,=,0.95, 95%CI: 0.9,0.99) and patients with smoking history who had concurrent diseases (OR,=,8.72, 95%CI: 1.53,49.52) had a higher risk of experiencing ADRs. Conclusion The rate of ADRs induced by cardiovascular drugs in this study was 24.2%. This study has shown that anti-arrhythmic and thrombolytic agents need more attention. Copyright © 2010 John Wiley & Sons, Ltd. [source] Adverse drug reactions in medical intensive care unit of a tertiary care hospital,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 7 2009Lisha Joshua MBBS Abstract Purpose Patients in the intensive care unit (ICU) have multiorgan dysfunction as well as altered pharmacokinetic parameters. Hence they are susceptible to adverse drug reactions (ADRs). The objective of the study is to assess the characteristics of ADRs among inpatients in the medical ICU and to compare the same with patients who have not experienced ADRs. Methods Prospective, observational study for a period of 1 year in medical ICU of a tertiary care hospital. Relevant data of patients with ADRS were analysed. Characteristics of patients with and without ADRs were compared. Results Of 728 patients admitted in medical ICU, 222 (28.4%) had ADRs. Multiple ADRs (38.7%) implicated by the same drug and serious ADRs (37%) were noticed. Renal/electrolyte system (21%) was most commonly involved. Clinical spectrum included acute renal failure (ARF, 11.4%), hepatic injuries (5.4%), haematological dysfunction (4.2%), seizures (3.3%), upper gastrointestinal bleed (3.3%) and cutaneous ADRs (3.3%). Antimicrobials (27%) were the commonly implicated drug class. The most commonly implicated drug was furosemide (6.8%). Infrequently reported ADRs included azithromycin-induced erythema multiforme, leflunamide-induced erythema multiforme and vasculitis, ceftazidime-induced seizures and ceftriaxone-induced hepatitis. Co-morbidity, polypharmacy and duration of stay were significantly higher in patients with ADRs compared to those who have not experienced ADRs. Three patients died. Conclusion High incidence of serious and multiple ADRs noticed. A wide clinical spectrum of ADRs and infrequently reported ADRs to newer drugs were also observed. Copyright © 2009 John Wiley & Sons, Ltd. [source] Adverse drug reactions in patients in an Iranian department of internal medicine,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 2 2009Sara Pourseyed MD Abstract Purpose Adverse drug reactions (ADRs) are a major cause of hospital admission and inpatient morbidity. The department of internal medicine is not an exception to this issue. This study was performed to determine the nature and frequency of ADRs in an internal medicine ward in Iran. Methods This survey was a prospective observational study based on admissions of 400 patients to the internal medicine ward over a 15-week period. Patients were intensively followed in order to assess any ADR as a cause of admission or occurring during hospitalization. Any suspicious ADR was confirmed by a pharmacist/pharmacologist. Results There were 47 patients of 400 patients (11.75%) that experienced at least one ADR. ADR leading to the admission was seen in seven cases (1.75%) and in 40 (10%) it occurred during hospitalization. ADRs were identified as preventable reactions in 50% of cases and as predictable in 94.3%. The severity of 18.6% of the ADRs was identified as mild, 62.9% as moderate, 14.3% as severe and 4.3% as lethal. Gastrointestinal system disorders (44.3%) represented the most frequent ADRs. The therapeutic groups that most commonly associated with suspected ADRs were antineoplastic, immunosuppressive and medicines used in palliative care (54.8%). Conclusions ADRs are common among hospitalized patients in department of internal medicine and can be severe and even lethal. Since most ADRs occurred during hospitalization in studied patients and half of them were preventable, prevention strategies should be considered in hospitals. Also, our findings confirmed the role of hospital pharmacists in the reducing ADRs. Copyright © 2008 John Wiley & Sons, Ltd. [source] Adverse effects of neuromuscular blocking agents based on yellow card reporting in the U.K.: are there differences between males and females?,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 3 2006FRCA, Karen Patricia Light MBBS Abstract Background Adverse drug reactions (ADRs) are known to occur during anaesthesia; in the U.K. such ADRs may be reported through the Yellow Card Scheme (YCS). Our aim was to determine the demographics of ADRs to neuromuscular blocking drugs without formal causality assessment. Methods A retrospective analysis of ADRs to seven neuromuscular blocking drugs reported via the YCS during a greater than 30-year period was performed. Sex and age were analysed in order to identify at risk groups. Results Of 998 reports, 969 included gender. Non-allergic suspected reactions occurred with almost the same frequency as those with an allergic component. The majority occurred in females 676 (70%), and significant sex differences were measured between drugs. Males were more likely to have suffered an ADR to atracurium (p,=,0.01) whilst females experienced more ADRs to suxamethonium (p,=,0.01). ADRs proved fatal in 81 (9%) of the 950 reports for single drugs. Mortality following suxamethonium was significantly higher in males at 22% compared with 9% females (p,<,0.001). More women than men were reported to have allergic reactions, 73% (362/499) compared with 27% (137/499) respectively. The female:male ratio for ADRs was reversed for subjects <,10 years compared with peak ADR reports during the decade from 31,40 years. Conclusions Sex differences in mortality exist in this analysis. The unexpected high frequency of non-allergic ADRs suggests that morbidity and mortality from reactions to established drugs is twice that expected from allergic reactions alone. Standards and guidance for the reporting of ADRs warrant urgent development. Copyright © 2006 John Wiley & Sons, Ltd. [source] Adverse drug reactions and off-label prescribing for paediatric outpatients: a one-year survey of spontaneous reports in SwedenPHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 3 2004Mike Ufer MD Abstract Purpose To investigate the extent and characteristics of off-label prescribing for paediatric outpatients among drugs reported to have caused an adverse reaction. Methods A retrospective, cross-sectional, observational analysis of spontaneous adverse drug reaction (ADR) reports in Sweden in the year 2000. We included all reports concerning drugs prescribed for outpatients younger than 16 years. Each ADR was classified with respect to its causality, seriousness and type of reaction. Off-label prescribing was evaluated with respect to age, dose, indication, formulation and route and frequency of administration. Results We identified 112 patient-linked reports corresponding to 158 ADRs of which 31% were serious. Antiasthmatic drugs were most frequently suspected as a cause of almost every third adverse reaction. The average proportion of off-label drug prescribing amounted to 42.4%. It was more frequently associated with serious than non-serious ADRs and mostly due to a non-approved age or dose. The most common clinical manifestations were psychiatric disorders and mucocutaneous inflammatory reactions. Conclusions Off-label prescribing for paediatric outpatients is common among drugs reported to have caused an ADR. It is suggested to further identify unlabelled drugs frequently contributing to, in particular serious ADRs in children for a proper benefit-risk assessment of off-label drug use. Copyright © 2003 John Wiley & Sons, Ltd. [source] Adverse drug reactions, MedWatch reporting and medical student educationPHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 2 2003Lionel D. Lewis MB BCh No abstract is available for this article. [source] Adverse drug reactions in adult medical inpatients in a South African hospital serving a community with a high HIV/AIDS prevalence: prospective observational studyBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 3 2008Ushma Mehta What is already known about this subject ,,Studies conducted primarily in developed countries have shown that adverse drug reactions (ADRs) are a significant cause of hospital admission, prolong hospital stay and consequently increase the cost of disease management in patients. ,,Cardiovascular medicines, hypoglycaemic agents, nonsteroidal anti-inflammatory drugs and antibiotics are the most frequently implicated medicines in these studies. ,,A large proportion of these ADRs have been shown to be preventable through improved drug prescribing, administration and monitoring for adverse effects. What this paper adds ,,This is the first Sub-Saharan African study in the HIV/AIDS era that describes the contribution of ADRs to patient morbidity, hospitalisation and mortality. ,,Cardiovascular medicines and antiretroviral therapy contributed the most to community-acquired ADRs at the time of hospital admission while medicines used for opportunistic infections (such as antifungals, antibiotics and antituberculosis medicines were most frequently implicated in hospital acquired ADRs. ,,ADRs in HIV-infected patients were less likely to be preventable. Aims To describe the frequency, nature and preventability of community-acquired and hospital-acquired adverse drug reactions (ADRs) in a South African hospital serving a community with a high prevalence of human immunodeficiency virus (HIV)/ acquired immunodeficiency syndrome. Methods A 3-month prospective observational study of 665 adults admitted to two medical wards. Results Forty-one (6.3%) patients were admitted as a result of an ADR and 41 (6.3%) developed an ADR in hospital. Many of the ADRs (46.2%) were considered preventable, although less likely to be preventable in HIV-infected patients than in those with negative or unknown HIV status (community-acquired ADRs 2/24 vs. 35/42; P < 0.0001; hospital-acquired ADRs 3/25 vs. 14/26; P = 0.003). Patients admitted with ADRs were older than patients not admitted with an ADR (median 53 vs. 42 years, P = 0.003), but 60% of community-acquired ADRs at hospital admission were in patients <60 years old. Among patients <60 years old, those HIV infected were more likely to be admitted with an ADR [odds ratio (OR) 2.32, 95% confidence interval (CI) 1.17, 4.61; P = 0.017]. Among HIV-infected patients, those receiving antiretroviral therapy (ART) were more likely to be admitted with an ADR than those not receiving ART (OR 10.34, 95% CI 4.50, 23.77; P < 0.0001). No ART-related ADRs were fatal. Antibiotics and drugs used for opportunistic infections were implicated in two-thirds of hospital-acquired ADRs. Conclusions ADRs are an important, often preventable cause of hospitalizations and inpatient morbidity in South Africa, particularly among the elderly and HIV-infected. Although ART-related injury contributed to hospital admissions, many HIV-related admissions were among patients not receiving ART, and many ADRs were associated with medicines used for managing opportunistic infections. [source] Antipsychotic-induced weight gainDIABETES OBESITY & METABOLISM, Issue 5 2005A. J. Goudie Abstract:, Novel ,atypical' antipsychotic drugs represent a substantial improvement on older ,typical' drugs. However, clinical experience has shown that some, but not all, of these drugs can induce substantial weight gain. This interferes with compliance with drug taking and has expected effects on morbidity and mortality. In this review, we summarize current thinking on: (i) the extent to which different ,atypical' drugs induce weight gain; (ii) the possible roles of various neurotransmitters and neuropeptides in this adverse drug reaction; and (iii) the state of development of animal models in this area. We also outline major areas for future research. [source] Efficacy of four insect repellents against mosquito bites: a double-blind randomized placebo-controlled field study in SenegalFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 5 2009Bernard Uzzan Abstract Insect-borne diseases represent a worldwide threat. In addition to fight against vectors (insecticides) and disease prevention (vaccination against yellow fever, chemoprophylaxis against malaria), insect repellents applied on the skin could help reduce the heavy burden related to these diseases. In a field study performed in Senegal, we compared the efficacy of one skin application between 3 and 4 p.m. of four spray repellents [icaridine 20%, para-menthane-diol (PMD) 20% and 50% and DEET 50%] against placebo, among 100 healthy male and female volunteers experienced with mosquito capture. Double-blind randomized cross-over placebo-controlled study (Latin-square design) during five consecutive nights (7 p.m. to midnight) in two villages was conducted. To avoid residual effect, right or left leg was alternately exposed during consecutive nights and the exposed leg was washed before next night. The statistical model was random and mixed effects anova. All four active repellents provided a significant and similar protection compared with placebo, lasting 8 h. However, there was a non-significant trend for a higher protection by DEET 50% than by PMD 20% (P = 0.07). Duration of protection was similar for all repellents. Their effects were similar among men and women, and against Anopheles or other species. No serious adverse drug reaction was noticed. Using a rigorous methodology and a large number of volunteers, our well-controlled study demonstrated an important and similar protective effect of all four repellents compared with placebo. Such field studies should be required before approval of any newly developed repellent. [source] The application of knowledge discovery in databases to post-marketing drug safety: example of the WHO databaseFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 2 2008A. Bate Abstract After market launch, new information on adverse effects of medicinal products is almost exclusively first highlighted by spontaneous reporting. As data sets of spontaneous reports have become larger, and computational capability has increased, quantitative methods have been increasingly applied to such data sets. The screening of such data sets is an application of knowledge discovery in databases (KDD). Effective KDD is an iterative and interactive process made up of the following steps: developing an understanding of an application domain, creating a target data set, data cleaning and pre-processing, data reduction and projection, choosing the data mining task, choosing the data mining algorithm, data mining, interpretation of results and consolidating and using acquired knowledge. The process of KDD as it applies to the analysis of spontaneous reports can be exemplified by its routine use on the 3.5 million suspected adverse drug reaction (ADR) reports in the WHO ADR database. Examples of new adverse effects first highlighted by the KDD process on WHO data include topiramate glaucoma, infliximab vasculitis and the association of selective serotonin reuptake inhibitors (SSRIs) and neonatal convulsions. The KDD process has already improved our ability to highlight previously unsuspected ADRs for clinical review in spontaneous reporting, and we anticipate that such techniques will be increasingly used in the successful screening of other healthcare data sets such as patient records in the future. [source] Neutropenia, thrombocytopenia and hepatic injury associated with dexketoprofen trometamol therapy in a previously healthy 35-year-old womanJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 1 2008S. Zabala MD Summary This case report describes a previously healthy 35-year-old woman, with an episode of fever, neutropenia, thrombocytopenia and elevation of biochemical markers of liver injury, 10 days after beginning drug therapy with dexketoprofen trometamol. Infectious and autoimmune causes of neutropenia, and viral or autoimmune hepatitis were excluded. The resolution following withdrawal of dexketoprofen trometamol confirms the possibility of an adverse drug reaction. [source] Cutaneous adverse drug reaction induced by a generic substitute of Zyloric® with a residual sensitization to allopurinolALLERGY, Issue 12 2006M.-L. Chandeclerc No abstract is available for this article. [source] Influence of genetic variation in CYP3A4 and ABCB1 on dose decrease or switching during simvastatin and atorvastatin therapy,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 1 2010Matthijs L. Becker PharmD Abstract Purpose Simvastatin and atorvastatin are metabolized by the CYP3A4 enzyme and transported by the ABCB1 transporter. We studied whether the polymorphism CYP3A4*1B and the polymorphisms C1236T, G2677A/T and C3435T in the ABCB1 gene were associated with a decrease of the prescribed dose or a switch to another cholesterol lowering drug during simvastatin and atorvastatin therapy. These events may indicate that statin plasma levels were too high and resulted in an adverse drug reaction or a too strong reduction in cholesterol level. Methods We identified 1239 incident simvastatin and atorvastatin users in the Rotterdam Study, a population-based cohort study. Associations between the polymorphisms in the CYP3A4 and ABCB1 gene and the time to a decrease in dose or a switch to another cholesterol lowering drug were studied using Cox proportional hazards. Results Simvastatin and atorvastatin users with the CYP3A4*1B variant G allele had a lower risk (HR 0.46; 95%CI 0.24,0.90) for these events than users with the wild-type AA genotype. No significant associations were found for the ABCB1 polymorphisms. The association with the CYP3A4*1B polymorphism was found in women (HR 0.33; 95%CI 0.12,0.89) and was non-significant in men (HR 0.69 95%CI 0.28,1.70). This association was stronger in patients with the ABCB1 3435T variant allele versus the G allele. Conclusion In simvastatin and atorvastatin users, the CYP3A4*1B G allele is associated with a lower risk of elevated statin plasma levels, particularly in women and in users with the ABCB1 3435T variant allele. Copyright © 2009 John Wiley & Sons, Ltd. [source] Adverse drug reaction-related hospitalisations: a population-based cohort studyPHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 4 2008Cornelis S. van der Hooft MD Abstract Purpose To evaluate the extent, characteristics and determinants of adverse drug reaction (ADR)-related hospitalisations on a population-based level in 2003. Methods We performed a cohort study in the Integrated Primary Care Information (IPCI) database, a general practitioners (GPs) research database with longitudinal data from electronic patient records of a group of 150 GP throughout the Netherlands. Hospital discharge letters and patient records were reviewed to evaluate ADR-related hospitalisations applying WHO causality criteria. The prevalence of ADR-related hospitalisations per total admissions and the incidence per drug group were calculated. Avoidability and seriousness of the ADRs causing admission were assessed applying the algorithm from Hallas. Results We identified 3515 hospital admissions, 1277 elective and 2238 acute. Of the acute admissions, 115 were caused by an ADR giving a prevalence of 5.1% (95% confidence intervals (CI): 4.3,6.1%). The prevalence of ADR-related acute admissions increased with age up to 9.8% (95%CI: 7.5,12.7) for persons >75 years. The ADRs that most frequently caused hospitalisations were gastro-intestinal bleeding with anti-thrombotics, bradycardia/hypotension with cardiovascular drugs and neutropenic fever with cytostatics. The incidence rate of ADR-related hospitalisations per drug group was highest for anti-thrombotics and anti-infectives and was relatively low for cardiovascular drugs. Fatality as a direct consequence of the ADR-related admission was 0.31%. In elderly patients 40% of the ADRs causing hospitalisation were judged to be avoidable. Conclusions The extent and potential avoidability of ADR-related hospitalisations is still substantial, especially in elderly patients. Measures need to be put into place to reduce the burden of ADRs. Copyright © 2008 John Wiley & Sons, Ltd. [source] Reporting of adverse drug reactions: predictors of under-reporting in Malaysia,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 2 2007Zoriah Aziz PhD Abstract Background Malaysia like many other countries worldwide uses spontaneous reporting systems as a mean of collecting data on suspected adverse drug reaction (ADR). However, compared to other countries, which use the system, the reporting rate in Malaysia is very low. Why some physicians do not report ADRs is not well understood. Objective To identify factors, which would predict physicians' failure to send ADR reports. Design and Setting Face-to-face interview using a structured questionnaire involving physicians working at the University of Malaya Medical Centre, Malaysia. Results About a third of the physicians in the Centre participated. Sixty-five of the 415 approached refused to participate. A high proportion of the respondents (81.4%) indicated that they had suspected an ADR but did not report it, while about 40% of the respondents were not aware of the existence of the national reporting system in Malaysia. Logistic regression modelling identified the variable ,ADR considered to be too trivial or too well known to report' as the strongest predictor of not reporting, followed by physicians' category and uncertainty that the reaction had been definitely caused by a drug. Conclusion Important predictor variables, which limit physicians from reporting ADR in Malaysia, were related to uncertainty of types of reaction to report, lack of awareness about the existence, function and purpose of national ADR reporting. The findings could be useful for planning strategies to improve the reporting rate. Copyright © 2006 John Wiley & Sons, Ltd. [source] Introducing triage logic as a new strategy for the detection of signals in the WHO Drug Monitoring Database,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 6 2004M. Ståhl Abstract Purpose An important role for the WHO Programme for International Drug Monitoring is to identify signals of international drug safety problems as early as possible. The signal detection strategy, operated at the Uppsala Monitoring Centre (UMC), gave too many drug,adverse drug reaction (ADR) combinations for individual review. Therefore additional selection strategies were needed to improve the likely signal-to-noise ratio and for the UMC to complement the efforts of national centres in an efficient way. Methods The combinations database of the first quarter of 2001 was analysed using algorithms representing different strategies for finding relevant signals using triage logic. Results The strategies that together gave a manageable number of combinations, i.e. around 600, for further consideration in a single quarter were the algorithms for ,Rapid reporting increase', ,Serious reaction and new drug' and ,Special interests'. These filters began to be used routinely on the combinations database in late 2001. Conclusions While stressing that human review is essential, triage strategies are useful when attempting analysis of large amounts of data. By definition, the use of triage strategies may exclude some potential signals from consideration, although the intention is to improve the chances of detection by focussing on areas of greatest importance. Copyright © 2004 John Wiley & Sons, Ltd. [source] Adverse drug reactions and off-label prescribing for paediatric outpatients: a one-year survey of spontaneous reports in SwedenPHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 3 2004Mike Ufer MD Abstract Purpose To investigate the extent and characteristics of off-label prescribing for paediatric outpatients among drugs reported to have caused an adverse reaction. Methods A retrospective, cross-sectional, observational analysis of spontaneous adverse drug reaction (ADR) reports in Sweden in the year 2000. We included all reports concerning drugs prescribed for outpatients younger than 16 years. Each ADR was classified with respect to its causality, seriousness and type of reaction. Off-label prescribing was evaluated with respect to age, dose, indication, formulation and route and frequency of administration. Results We identified 112 patient-linked reports corresponding to 158 ADRs of which 31% were serious. Antiasthmatic drugs were most frequently suspected as a cause of almost every third adverse reaction. The average proportion of off-label drug prescribing amounted to 42.4%. It was more frequently associated with serious than non-serious ADRs and mostly due to a non-approved age or dose. The most common clinical manifestations were psychiatric disorders and mucocutaneous inflammatory reactions. Conclusions Off-label prescribing for paediatric outpatients is common among drugs reported to have caused an ADR. It is suggested to further identify unlabelled drugs frequently contributing to, in particular serious ADRs in children for a proper benefit-risk assessment of off-label drug use. Copyright © 2003 John Wiley & Sons, Ltd. [source] Proton pump inhibitor-induced acute interstitial nephritisBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 6 2007Linda Härmark What is already known about this subject ,,In several case reports the use of omeprazole has been associated with interstitial nephritis. ,,Recently there have been reports linking other proton pump inhibitors (PPIs) with interstitial nephritis. What this study adds ,,We present supplementary cases received by the Netherlands Pharmacovigilance Centre Lareb, concerning interstitial nephritis in users of PPIs including omeprazole, pantoprazole and rabeprazole. ,,In this case series seven patients are presented. In six cases they recovered spontaneously after cessation of the PPI, in one case the patient recovered after treatment with a corticosteroid. ,,Further support for this association comes from the worldwide adverse drug reaction database of the World Health Organization. ,,This report shows that interstitial nephritis can occur with all PPIs. Health professionals should be aware of this potential serious adverse drug reaction. Aim To investigate the association between the use of proton pump inhibitors (PPIs) and acute interstitial nephritis (AIN). Methods The Netherlands Pharmacovigilance Centre Lareb received seven case reports of AIN induced by various PPIs. In five of the reports it was mentioned that the diagnosis was confirmed by a renal biopsy. Results The time to onset varied between hours to 4 months. In all cases but one the patient spontaneously recovered after withdrawal of the offending agent. In one case the patient received treatment with prednisolone and recovered. In one patient a rechallenge was done 9 days after the initial event. Within 12 h of re-exposure the patient developed symptoms of AIN. Conclusions The mechanism of drug-induced AIN is unknown, but an immunological mechanism is suspected. Our reports show no relation between dosage, latency, time to recovery, age or gender, supporting the hypothesis that the aetiology of AIN is immunological. Lareb has received reports of AIN with the use of omeprazole, pantoprazole and rabeprazole. This shows that AIN is a complication associated with the whole group of PPIs and not only omeprazole. It is important for health professionals to be aware of this adverse drug reaction, because an accurate and timely diagnosis and withdrawal of the offending drug can prevent potentially life-threatening renal failure. [source] Clindamycin and taste disordersBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 4 2007Mark C. H. De Groot What is already known about this subject. ,,The antibiotic clindamycin has a bitter taste when it is used orally. What this study adds ,,A case series on oral as well as i.v. use of clindamycin associated with taste disorders is presented. ,,After corrections in a case-by-case analysis for several possible confounders such as indication, clindamycin is disproportionally associated with taste disorders. ,,Serum and hence saliva and sputum clindamycin levels seem to be responsible for this reversible adverse drug reaction. Aims Topical use of clindamycin has been associated with taste disorders in the literature, but little is known about the nature of this adverse drug reaction. The aim of this article was to describe reports of clindamycin-induced taste disorders and to analyse the factors involved. Methods The adverse drug reaction database of the Netherlands Pharmacovigilance Centre was searched for reports concerning taste disorders with antibiotics. Clinical review of the cases and statistical analysis with logistic regression were performed. Characteristics of patients who reported taste disorders were compared for age, gender and formulation in clindamycin vs. other antibiotic users. Results Taste disorders were reported in seven (18%) of the clindamycin cases. In five reports an oral formulation was involved, in one report intravenous (i.v.) administration and in one report both formulations were used. Latency was <1 day after start and in one case taste disorders were present repeatedly at 10 min after every i.v. application. The adjusted reporting odds ratio was 7.0 (95% confidence interval 2.8, 17.3) and supports a possible causal relationship. Conclusions The association of clindamycin and taste disorders is supported by disproportionality analysis and seems to be independent of possible confounders such as age, gender and infections. The case reports suggest a role for clindamycin concentrations excreted in body fluids like saliva. [source] Recording previous adverse drug reactions,a gap in the systemBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 6 2001Gillian M. Shenfield Aims, To measure the accuracy of recording of previous adverse drug reaction (ADR) history in patients admitted to a teaching hospital before and after an education programme. Methods, One month survey of patients on one medical and one surgical ward, repeated after a 1 month education programme. Patients answered a questionnaire about previous ADRs and this information was compared with that in all relevant sections of their medical records and medication charts. Results, Of 117 patients at baseline, 50 had a total of 81 previous ADRs. Only 75% were recorded on medication charts and 57% and 64%, respectively, in medical and nursing notes. In the post education survey of 124 patients, 56 had 105 previous ADRs, 85% were recorded on medication charts and 64% and 70% in medical and nursing records. These differences were not significant. Serious ADRs were also poorly recorded at baseline but, due to intervention by ward pharmacists, their recording on medication charts improved significantly after education. Pharmacists also significantly improved the quality of description of previous ADRs in both parts of the study. Conclusions, Previous ADR history obtainable from hospital patients is poorly recorded in medical records and an intensive education programme only produced a significant change in recording by ward pharmacists. Better strategies are needed to improve this essential aspect of history taking. [source] Intranasal fentanyl in 1,3-year-olds: A prospective study of the effectiveness of intranasal fentanyl as acute analgesiaEMERGENCY MEDICINE AUSTRALASIA, Issue 5 2009Joanne Cole Abstract The primary objective of the present study was to determine the effectiveness of intranasal fentanyl analgesia in children aged 1,3 years with acute moderate to severe pain presenting to the ED. We also aimed to gather information on the safety and acceptability of intranasal fentanyl in this age group. Two paediatric ED enrolled children aged 1,3 years, with acute moderate or severe pain. Intranasal fentanyl was administered (1.5 µg/kg) via a mucosal atomiser device using a 50 µg/mL solution of fentanyl. Physiological parameters (heart rate, respiratory rate, oxygen saturations and level of consciousness) were measured at regular intervals. Objective pain assessment was completed using the Faces, Legs, Arms, Cry, Consolability (FLACC) score. Forty-six children presenting with acute moderate to severe pain were included. The median FLACC score before intranasal fentanyl administration was 8 (interquartile range [IQR] 5,10), decreasing to 2 (IQR 0,4) 10 min post fentanyl (P < 0.0001) and 0 (IQR 0,2) 30 min post fentanyl (P < 0.0001). A clinically significant decrease in FLACC scores was seen in 93% of children 10 min post fentanyl administration and 98% of children 30 min post fentanyl. Intranasal fentanyl delivery using a mucosal atomiser was well tolerated by all children. There were no adverse drug reactions or adverse events detected. Intranasal fentanyl is an effective, safe and well-tolerated mode of analgesia for children aged 1,3 years with moderate to severe pain. [source] Experience in adverse events detection in an emergency department: Nature of eventsEMERGENCY MEDICINE AUSTRALASIA, Issue 1 2007James Hendrie Abstract Objective:, The study was performed to determine the nature of adverse events in an ED. Methods:, The methodology has been described in the accompanying paper. Two by two tables were analysed using the two-tailed Fisher's exact test. A P -value of ,0.05 was considered significant. Statistical analysis was performed using MINITAB. Results:, One hundred and ninety-four events were detected, from a sample of 3222 patients. Except where specified, events with management causation ,3 were excluded. This excluded 24 events (12.4%) leaving 170 for analysis. Errors of commission occurred in 55% and omission in 45%. Errors of commission were significantly associated with prior events, errors of omission with ED events (P , 0.0001, respectively). The most common cause of events was drug reactions. 1.35% had a Naranjo score , 1, 0.54% , 4. Prior events were significantly associated with adverse drug reactions (P , 0.0001). Drug reactions were associated with a lower preventability score (P , 0.0001). Diagnostic issues were present in 1.2%. All three categories, that is diagnosis not considered, diagnosis within the differential and seriousness not appreciated were associated preventability ,4 (P , 0.0001, P , 0.02 and P , 0.004, respectively). Diagnostic problems were significantly associated with ED events (P , 0.0001). Conclusion:, In conclusion, the data demonstrate that events fall into two sets: prior events which are associated with errors of commission, drug reactions and lower preventability; and ED events which are associated with errors of omission, diagnostic issues and high preventability. [source] The clinical impact of pharmacogenetics on the treatment of epilepsyEPILEPSIA, Issue 1 2009Wolfgang Löscher Summary Drug treatment of epilepsy is characterized by unpredictability of efficacy, adverse drug reactions, and optimal doses in individual patients, which, at least in part, is a consequence of genetic variation. Since genetic variability in drug metabolism was reported to affect the treatment with phenytoin more than 25 years ago, the ultimate goal of pharmacogenetics is to use the genetic makeup of an individual to predict drug response and efficacy, as well as potential adverse drug events. However, determining the practical relevance of pharmacogenetic variants remains difficult, in part because of problems with study design and replication. This article reviews the published work with particular emphasis on pharmacogenetic alterations that may affect efficacy, tolerability, and safety of antiepileptic drugs (AEDs), including variation in genes encoding drug target (SCN1A), drug transport (ABCB1), drug metabolizing (CYP2C9, CYP2C19), and human leucocyte antigen (HLA) proteins. Although the current studies associating particular genes and their variants with seizure control or adverse events have inherent weaknesses and have not provided unifying conclusions, several results, for example that Asian patients with a particular HLA allele, HLA-B*1502, are at a higher risk for Stevens-Johnson syndrome when using carbamazepine, are helpful to increase our knowledge how genetic variation affects the treatment of epilepsy. Although genetic testing raises ethical and social issues, a better understanding of the genetic influences on epilepsy outcome is key to developing the much needed new therapeutic strategies for individuals with epilepsy. [source] Pharmacogenomics in dermatology: from susceptibility genes to personalized therapyEXPERIMENTAL DERMATOLOGY, Issue 4 2009Carlo Pincelli Abstract:, A significant proportion of patients with skin disease do not respond to treatment and adverse drug reactions are a common problem. Genetic factors are important determinants for both drug efficacy and toxicity. The fields of pharmacogenetics and pharmacogenomics examine inter-individual variations in the DNA sequence that are related to drug efficacy and toxicity. Here, we present pharmacogenomic data relevant to dermatology and explore the role of dermatologists in identifying patients who may respond to treatment or experience adverse drug reactions. [source] Dextropropoxyphene withdrawal from a French university hospital: impact on analgesic drug consumptionFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 2 2009Sabine Gaubert Abstract Dextropropoxyphene is a weak opioid analgesic, widely used as a step 2 analgesic (according to WHO classification) in combination with peripheral analgesics, mainly paracetamol. Recent data have underlined its poor analgesic efficacy (in comparison with paracetamol), risks of serious adverse drug reactions (i.e. hepatic reactions, hallucinations, abuse, withdrawal symptoms, hypoglycaemia), possible lethality after overdose, its risk of accumulation in patients with renal failure or in elderly people and some pharmacokinetic insufficiencies (i.e. different half-lives for dextropropoxyphene and paracetamol). Taking into account these data, the drug committee of the Toulouse University Hospital (France) decided to withdraw dextropropoxyphene from the hospital formulary since 1 June 2005. The aim of our study was to investigate the consequences of this withdrawal by comparing use of analgesic drugs in Toulouse University Hospital before (2004) and after (2006) dextropropoxyphene withdrawal (using defined daily dose for 1000 hospitalization-days as the unit measure). Before withdrawal, dextropropoxyphene (in combination with paracetamol) was the second most used analgesic drug after paracetamol alone. After dextropropoxyphene withdrawal, total consumption of analgesic drugs decreased by 4.6% (2006 vs. 2004). There was a 28% decrease in consumption of step 2 analgesics [with an increase in oral tramadol and a slight decrease in codeine (in combination with paracetamol)]. During the same period, step 1 analgesic consumption increased by 11% (mainly paracetamol) and that of step 3 analgesics slightly decreased (,8%). These results show that dextropropoxyphene withdrawal was not associated with a marked switch in prescriptions towards other analgesic drugs. This paper underlines the interest of a hospital-based drug committee to promote rational drug use. Finally, the present data allow us to discuss putative misuse of dextropropoxyphene. [source] | ||||||||||||||||||||||||||||||||||