Dose adjustment in renal impairment - Response from AHFS Drug Information

BMJ (online) (Impact Factor: 16.38). 08/2005; 331(7511):293. DOI: 10.1136/bmj.331.7511.293
Source: PubMed
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    ABSTRACT: Drug repositioning, also known as drug repurposing or reprofiling, is the process of finding new indications for established drugs. Because drug repositioning can reduce costs and enhance the efficiency of drug development, it is of paramount importance in medical research. Here, we present a systematic computational method to identify potential novel indications for a given drug. This method utilizes some prior knowledge such as 3D drug chemical structure information, drug-target interactions and gene semantic similarity information. Its prediction is based on another form of 'expression profile', which contains scores ranging from -1 to 1, reflecting the consensus response scores (CRSs) between each drug of 965 and 1560 proteins. The CRS integrates chemical structure similarity and gene semantic similarity information. We define the degree of similarity between two drugs as the absolute value of their correlation coefficients. Finally, we establish a drug similarity network (DSN) and obtain 33 modules of drugs with similar modes of action, determining their common indications. Using these modules, we predict new indications for 143 drugs and identify previously unknown indications for 42 drugs without ATC codes. This method overcomes the instability of gene expression profiling derived from experiments due to experimental conditions, and predicts indications for a new compound feasibly, requiring only the 3D structure of the compound. In addition, the high literature validation rate of 71.8% also suggests that our method has the potential to discover novel drug indications for existing drugs.
    Molecular BioSystems 03/2014; DOI:10.1039/c3mb70554d · 3.18 Impact Factor
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    ABSTRACT: Information about dosing adjustments in patients with chronic kidney disease is important to avoid toxicity for several medicines. The aim of our study was to assess the clinical relevance of the instructions for dose adjustment in patients with renal impairment provided in the Summaries of Product Characteristics (SmPCs) approved by the European Medicines Agency (EMA). SmPCs available on the EMA website on April 2011 were retrieved, and information on the elimination route and instructions for use in renal impairment was analysed independently by two of the authors. SmPCs were classified as containing 'explicit' or 'poor' information based on whether they presented (or not) instructions for use of the medicine in renal impairment. Information was considered 'relevant' if SmPCs provided clear instructions for dose adjustment. Of the 356 SmPCs analysed, 13.8 and 37.4 % were classified as providing poor information and explicit but not relevant information, respectively. Only 48.8 % SmPCs provided both explicit and relevant information on medicine use in renal impairment. No difference was found in the average time since last update among SmPCs classified as containing explicit or poor information, as well as those classified as containing relevant or not relevant information. Also, no association was found between the clinical relevance of the information and whether or not the medication was an orphan drug, and 80 % SmPCs did not provide information on the use of the medicine in patients undergoing haemodialysis. Based on our analysis, current versions of SmPCs are characterised by several information deficits and by containing recommendations that are not relevant to clinical practice in terms of dose adjustment in renal impairment. These shortcomings might limit their usefulness for healthcare professionals and integration into clinical decision-making support systems.
    European Journal of Clinical Pharmacology 07/2013; 69(11). DOI:10.1007/s00228-013-1560-2 · 2.70 Impact Factor
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    ABSTRACT: WHAT IS KNOWN AND OBJECTIVE: Prescribing sulfonamide-containing medications for patients with sulfonamide allergy continues to complicate medical decisions. We examined the cautionary recommendations in the approved drug monographs and primary literature, and formulated an evidence-based grading of cautionary recommendations for sulfonamide allergy and cross-reactivity among sulfonamide-containing medications. METHODS: Drug monographs were collected from six countries and three drug compendia. Two reviewers independently extracted the data from the contraindication, warning and/or precaution sections of drug monographs. Evidence for cross-reactivity was examined in the primary literature and compared with drug monograph recommendations. Consequently, medications were categorized based on the strength of recommendation and level of evidence by consensus. RESULTS AND DISCUSSION: We identified wide variability in cautionary recommendations ranging from no warning or precaution to contraindication among the sources reviewed. The recommendations were located mainly in the contraindication section of monographs for France (65·2%), United Kingdom (51·9%), Italy (50·0%), South Korea (43·5%), United States (38·2%) and Canada (37·0%), whereas in drug compendia, the recommendations were found in the precaution section for Martindale (51·4%) and Micromedex-Drugdex (33·3%), and contraindication and precaution section for the American Hospital Formulary Service Drug Information 2010 (30·8%). Evidence from the primary literature varied with recommendation included in drug monographs. Evidence-based categorization was carried out for 16 medications. Two sulfonamide-moiety-containing drugs were considered safe, six non-sulfonylarylamines required precaution, and eight medications from all three sulfonamide chemical classes were considered mostly unsafe. WHAT IS NEW AND CONCLUSION: There are significant discrepancies in cautionary recommendations included in drug-labels and drug compendia. Statements concerning cross-reactive hypersensitivity with other sulfonamides generally suggest theoretical possibilities. The consensus evidence-based grading instrument developed may be useful for deriving cautionary recommendations for sulfonamide-allergic patients.
    Journal of Clinical Pharmacy and Therapeutics 03/2013; DOI:10.1111/jcpt.12048 · 1.53 Impact Factor


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