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Spontaneous Reports (spontaneous + report)
Selected AbstractsSafety update on the use of recombinant factor VIIa and the treatment of congenital and acquired deficiency of factor VIII or IX with inhibitorsHAEMOPHILIA, Issue 5 2008T. ABSHIRE Summary., Recombinant factor VIIa (rFVIIa, NovoSeven®) has been licensed for treatment of haemophilia with inhibitors in Europe since 1996 and in North America since 1999. Overall, approximately 1.5 million doses have since been administered. Safety data from licensure to April 2003 revealed 25 thromboembolic (TE) adverse events (AE) from over 700 000 doses given, a remarkably low incidence of TE events. Recent reports have cited a higher prevalence of TE events with rFVIIa use, especially when used off-label. This report reviews the TE and fatal events with use of rFVIIa for congenital and acquired haemophilia A or B from May 2003 to December 2006. Approximately 800 000 standard doses of rFVIIa have been administered during this time frame. All clinical trials, spontaneous and solicited reports, as well as a detailed literature review, were included in the data analysis. There were a total of 30 TE events and 6 TE-associated fatal events. Spontaneous reports captured 14/71 (20%) TE/AE and 2/34 TE-associated/total fatal events. From solicited reports, 5/40 (12.5%) were associated with a TE and 1/32 TE-associated fatal events. Literature review revealed 11/19 (58%) TE events and 3/6 TE-associated fatal events. Despite the use of high-dose rFVIIa (270 ,g kg,1) in some clinical trials and registries, rFVIIa appears safe, when used for congenital and acquired haemophilia. The prevalence of TE associated with rFVIIa use is less than 4/100 000 and a TE-associated fatal event is also extremely rare. However, use of rFVIIa for off-label indications should continue to be monitored closely via clinical trials and carefully designed registries. [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] Telithromycin-associated hepatotoxicity: Clinical spectrum and causality assessment of 42 cases,HEPATOLOGY, Issue 1 2009Allen D. Brinker Telithromycin is the first of a new class of ketolide antibiotics with increased activity against penicillin-resistant and erythromycin-resistant pneumococci. This agent received approval by the United States Food and Drug Administration (FDA) in 2004 for treatment of upper and lower respiratory infections. Following market introduction, spontaneous reports of telithromycin-associated hepatotoxicity, including frank liver failure, were received. To address these reports, an ad hoc group with expertise in spontaneous adverse events reporting and experience in evaluating drug-induced liver injury was formed, including members of the FDA, other federal agencies, and academia. The primary objective of this group was to adjudicate case reports of hepatic toxicity for causal attribution to telithromycin. After an initial screening of all cases of liver injury associated with telithromycin reported to FDA as of April 2006 by one of the authors, 42 cases were comprehensively reviewed and adjudicated. Five cases included a severe outcome of either death (n = 4) or liver transplantation (n = 1); more than half were considered highly likely or probable in their causal association with telithromycin. Typical clinical features were: short latency (median, 10 days) and abrupt onset of fever, abdominal pain, and jaundice, sometimes with the presence of ascites even in cases that resolved. Concurrence in assignment of causality increased after agreement on definitions of categories and interactive discussions. Conclusion: Telithromycin is a rare cause of drug-induced liver injury that may have a distinctive clinical signature and associated high mortality rate. Consensus for attribution of liver injury to a selected drug exposure by individual experts can be aided by careful definition of terminology and discussion. (HEPATOLOGY 2009;49:250-257.) [source] Hypertrichosis in females applying minoxidil topical solution and in normal controlsJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 3 2003RPR Dawber ABSTRACT Background, Hypertrichosis has been reported more frequently in females than in males who use minoxidil topical solution (MTS) for the treatment of androgenetic alopecia (AGA). This article examines the occurrence of MTS-induced hypertrichosis in females. Methods, Data from placebo-controlled clinical trials in females (up to 5% MTS) were analysed based on spontaneous reports of hypertrichosis/facial hair and investigators' inquiries (solicited) about the presence of any new hair growth on body parts other than the scalp. A postmarketing drug surveillance database for MTS was also examined for reports of hypertrichosis/facial hair. Results, In the clinical trials involving a total of 1333 females, spontaneous reports of hypertrichosis/facial hair were noted for 50 (4%) females in a dose-related pattern of response (5% MTS > 2% MTS > placebo). Nine females (seven and two in the 5% MTS and 2% MTS groups, respectively) discontinued treatment because of hypertrichosis/facial hair. Solicited reports of excessive hair growth (primarily facial) also showed a dose-related pattern of response. Post-marketing data showed a lower occurrence (0.5%) of hypertrichosis/facial hair than in the clinical trials. Of interest, in one clinical trial, 27% of the females enrolled (MTS and placebo treated) had facial hair growth reported at baseline. Conclusions, Females with some hirsutism are particularly prone to seek treatment for AGA, and this may explain the high occurrence of hypertrichosis/facial hair found in the MTS clinical trials. Furthermore, some demographic groups of females are prone to develop facial hair and the problem of unwanted facial hair growth seems to be underestimated. Some females may have hair follicles that are very sensitive to MTS and should use the lowest strength of MTS (2%) to help avoid unwanted hair growth. The hypertrichotic effect of MTS on other sites than the scalp, including the face, is reversible and does not always require discontinuation of therapy. [source] Comparison of military and civilian reporting rates for smallpox vaccine adverse events,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 6 2007A. W. McMahon MD Abstract Introduction US smallpox vaccination (SMA) started most recently in December 2002. Military and civilian personnel report adverse events (AEs) to the Vaccine Adverse Event Reporting System (VAERS), a surveillance system that relies on spontaneous reports. Although reported rates of probable myo/pericarditis after SMA in the literature are similar between military personnel and civilian healthcare workers, some civilian AE reporting rates after SMA appeared higher than those in the military. Objective Determine if SMA-associated reporting rates are different in civilians than in the military, considering age, sex, seriousness, and expectedness of the AE, as well as self-reporting. Methods Numerators were SMA reports in VAERS from 12/12/02 to 3/1/04. Limitations of VAERS include underreporting and lack of diagnostic confirmation. Denominators were number of military and civilian vaccinees. Results Reporting rates stratified by age and sex of serious and non-serious AEs were significantly higher in civilian than military personnel ages <55 years (rate ratios 4,27). These rate ratios decreased with increasing age. Conclusions Reporting rates in VAERS differed significantly and substantially in civilians compared to military personnel <55 years of age. Differences in stimulated passive surveillance systems, and AE reporting practices, including the ,threshold' for reporting most likely explain these findings. These results suggest that in the case of smallpox vaccine AEs, there may be systematic differences in reporting completeness between the civilian and military sectors, and that passive surveillance data should be interpreted with caution. Copyright © 2006 John Wiley & Sons, Ltd. [source] Disproportionality analyses of spontaneous reportsPHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 8 2004Sean Hennessy PharmD No abstract is available for this article. [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] Biases affecting the proportional reporting ratio (PRR) in spontaneous reports pharmacovigilance databases: the example of sertindolePHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 4 2003Nicholas Moore Abstract Background Automated measures of reporting disproportionality in databases of spontaneous reports of adverse drug reactions are an emerging tool to identify drug-related alerts. Sertindole, a new atypical neuroleptic known to prolong the QT interval, was suspended in November 1998 because the proportion of reports of fatal reactions suggesting arrhythmia among all reports with sertindole was almost ten times higher than that for other atypical neuroleptics in the UK. This excess risk was not predicted in preclinical data and had not been found in premarketing trials. Method Reporting patterns over time were analysed. Prescription Event Monitoring (PEM) studies and a large retrospective cohort allowed for the comparison of actual death rates with atypical neuroleptics, and to assess which proportion of the deaths that occurred were reported. Results There were indications of possible skewing of reporting related to notoriety, surveillance and market size effects. Death rates in PEM studies were essentially similar between sertindole and other neuroleptics. Cardiac deaths had been two to three times more often reported than other causes of death. Conclusion Proportional reporting ratios indicate differential reporting of possible reactions, not necessarily differential occurrence. There was no indication of an actual increase of risk of all causes or cardiac deaths during sertindole treatment, but only an increased risk of its being reported. The suspension of sertindole was rescinded by Committee on Proprietary Medicinal Products (CPMP) in October 2001. Copyright © 2003 John Wiley & Sons, Ltd. [source] Latest news and product developmentsPRESCRIBER, Issue 4 2008Article first published online: 20 MAR 200 Suicide warning for all antidepressants All antidepressants are to include a warning of the risk of suicide in their product information, the MHRA says. The requirement formerly applied only to SSRIs but, following a US review of safety data, the Agency says the risk is similar for all classes of antidepressants. Patients at increased risk include young people with psychiatric morbidity and those with a history of suicidal ideation. Patients are at increased risk of suicide until remission occurs, and clinical experience shows that the risk is increased during the early stages of recovery. Confusion over type 2 diabetes management Contradictory findings have been reported from two studies of intensive management of type 2 diabetes. The STENO-2 study (N Engl J Med 2008;358:580-91) found that tight control of blood glucose, blood pressure and lipids plus low-dose aspirin in 160 patients with type 2 diabetes and microalbuminuria significantly reduced all-cause mortality, cardiovascular events, cardiovascular death and microvascular complications by 40-60 per cent. The US National Heart, Blood and Lung Institute has announced the end of the intensive treatment arm of the ACCORD study (unpublished). This study was comparing intensive lowering of blood glucose below currently recommended levels (target HbA1C <6 per cent) with conventional management in adults with type 2 diabetes at especially high risk for heart attack and stroke. Although mortality was reduced in both arms compared with other populations, intensive treatment was associated with increased mortality equivalent to three deaths per 1000 patients per year over four years. Another antibiotics campaign The Government has launched another campaign to promote public awareness that antibiotics are not appropriate for viral infections causing coughs, colds and sore throats. Get Well Soon , Without Antibiotics is supported by a national advertising campaign and leaflets and posters encouraging the public to ask advice rather than demand a prescription. Details are available at www.dh.gov.uk. Episenta: once-daily sodium valproate Following a launch to specialists last year, a new once-daily modified-release formulation of sodium valproate is being promoted more widely to GPs. Episenta is licensed for the treatment of all forms of epilepsy and is formulated as modified-release capsules of 150mg and 300mg and sachets of modified-release granules of 500mg and 1000mg. The dose may be administered once or twice daily. Patients may be switched from enteric-coated tablets of valproate to the same dose given as Episenta. Episenta costs £5.70 or £10.90 for 100 × 150mg or 300mg capsules, and £18 or £35.50 for 100 × 500mg or 1000mg sachets. Latest NICE agenda The Department of Health has referred a new batch of topics for appraisal by NICE. Six of seven technology appraisals are for cancer drugs; the last is for dabigatran etexilate for venous thromboembolism. There will be four new clinical guidelines: autism spectrum disorders, hypertension in pregnancy, bed-wetting in children and severe mental illness with substance abuse. Two combined public health and clinical guidelines will address alcohol misuse. Varenicline vs NRT Varenicline (Champix) offers slightly greater smoking cessation rates than nicotine replacement therapy (NRT) in the long term and better symptom improvement, an international study has shown (Thorax 2008; published online:10.1136/ thx.2007.090647). A total of 746 smokers were randomised to treatment with varenicline 1mg twice daily for 12 weeks or transdermal NRT (21mg reducing to 7mg per day) for 10 weeks. Continuous abstinence rates for the last four weeks of treatment were 56 vs 43 per cent. The corresponding rates for one year were 26 and 20 per cent. Varenicline was associated with greater reductions in cravings, withdrawal symptoms and smoking satisfaction, but more nausea (37 vs 10 per cent). Adverse reactions class effect of statins The MHRA has identified several adverse effects that it says are class effects of the statins (Drug Safety Update 2008;1:Issue 7). Following a review of clinical trials and spontaneous reports, it is now apparent that any statin may be associated with sleep disturbance, depression, memory loss and sexual dysfunction; interstitial lung disease has been reported rarely. Product information is being updated to include the new information. Depression, including suicidal ideation, has also been associated with varenicline (Champix), the MHRA says; affected patients should stop treatment immediately. The combination of transdermal nicotine replacement therapy (NRT) and varenicline appears to be associated with a higher incidence of nausea, headache, vomiting, dizziness, dyspepsia and fatigue than NRT alone. The MHRA has also announced that, following the suspension of marketing authorisation for carisoprodol (Carisoma), it is considering a phased withdrawal of the closely-related meprobamate , the main active metabolite of carisoprodol. Following a successful pilot study, the public are being encouraged to report adverse reactions on yellow cards; the MHRA notes that health professionals provide more complete reports but patients include more information about quality of life. The scheme will be promoted via community pharmacies throughout the UK from February 2008. Cochrane: evidence on back pain interventions The latest release of Cochrane reviews includes three meta-analyses assessing interventions for back pain. Overall, NSAIDs were found to be effective as short-term treatment for acute or chronic back pain but the effect size was small. They were comparable with paracetamol but associated with more adverse effects; COX-2 selective NSAIDs were similarly effective, with slightly fewer adverse effects. There was no evidence that antidepressants reduced back pain but intensive individual patient education (lasting 2.5 hours) was effective for acute and subacute back pain and comparable with manipulation and physiotherapy; its effects on chronic pain were unclear. Copyright © 2008 Wiley Interface Ltd [source] | ||||||||||