Analyses of Adverse Drug Reactions–Nationwide Active Surveillance Network: Canadian Pharmacogenomics Network for Drug Safety Database

Tanoshima, Reo; Khan, Amna; Biala, Agnieszka; Trueman, Jessica N; Drögemöller, Britt I.; Wright, Galen E.B.; Hasbullah, Jafar S.; Groeneweg, Gabriella; Ross, Colin J.D.; Carleton, Bruce

doi:10.1002/jcph.1336

Cited by 14 publications

(11 citation statements)

References 32 publications

(81 reference statements)

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“…Ototoxicity is one of the most commonly reported adverse drug reactions 1 . Symptoms of ototoxicity, such as hearing loss and vestibular dysfunction, profoundly impact quality of life and are a public health burden.…”

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confidence: 99%

Drug‐Induced Ototoxicity: A Comprehensive Review and Reference Guide

Rizk

Lee

Liu³

et al. 2020

Pharmacotherapy

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OBJECTIVE In an era of increasing polypharmacy, adverse drug effects such as ototoxicity have significant public health implications. Despite the availability of evidence, many health care professionals may not know the risk of ototoxicity in common medications. Therefore, the aim of this review is to provide a comprehensive, easy to use, ototoxic profile of medications with an assessment of supporting evidence. METHODS Medications of interest were identified through adverse drug reaction reports derived from Micromedex (IBM), Lexicomp (Wolters Kluwer), and the textbook, Drug Induced Diseases: Prevention, Detection, and Management. Additional evidence was identified though a query of PubMed and the Cochrane database. Evidence of causality was graded according to the following: A (randomized, controlled clinical trials), B (nonrandomized clinical trials, prospective observational studies, cohort studies, retrospective studies, case-controlled studies, and/or postmarketing surveillance studies), and C (case reports/case series). RESULTS A total of 194 systemically administered medications associated with ototoxicity were identified, most commonly antimicrobials (53), psychotropics (21), antihypertensive/antiarrhythmics (19), nonsteroidal antiinflammatory drugs (18), and antineoplastics (16). There was evidence of cochleotoxicity in 165 medications (evidence grading A [22], B [77], C [69]), vestibulotoxicity in 100 medications (evidence grading A [23], B [47], and C [30]), and dizziness in 142 medications (evidence grading A [50], B [76], and C [16]). In addition, a review of the evidence of ototoxicity in ototopical medications is also reviewed. CONCLUSION The effect and severity of ototoxicity can vary immensely depending on pharmacological and individual patient risk factors. The intent of this comprehensive review was to help health care providers of all sectors obtain a deeper knowledge of drug-induced ototoxicity to make more informed management decisions for their patients.

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confidence: 99%

Drug‐Induced Ototoxicity: A Comprehensive Review and Reference Guide

Rizk

Lee

Liu³

et al. 2020

Pharmacotherapy

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“…The individuals carrying nonactive alleles are classified as “predicted” poor metabolizers with no metabolic capacity for these enzymes. On the contrary, individuals with more than two active alleles have been associated with increased enzyme activity [14]. There are two risk scenarios in regards to the genetic background: the first is the administration of a prodrug that requires conversion to an active metabolite where slow metabolizers generate loss of efficacy.…”

Section: Discussionmentioning

confidence: 99%

“…Our population exhibited variability in CNVs: 50% of individuals carried deletions and duplications while 39% had a unique type of CNV (deletion or duplication). According to the number of CYP-450 or GST active copies, the individuals can be potentially defined as poor metabolizers (PM) or ultrarapid metabolizers (UM) [14]. We identified that 83% of the analyzed individuals presented CNVs in one or several of the CYP-450 and / or GST genes studied.…”

Section: Introductionmentioning

confidence: 99%

Copy number variation profiling in pharmacogenetics CYP-450 and GST genes in Colombian population

et al. 2019

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Background: Copy Number variation (CNVs) in genes related to drug absorption, distribution, metabolism and excretion (ADME) are relevant in the interindividual variability of drug response. Studies of the CNVs in ADME genes in Latin America population are lacking. The objective of the study was to identify the genetic variability of CNVs in CYP-450 and GST genes in a subgroup of individuals of Colombian origin. Methods: Genomic DNA was isolated from 123 healthy individuals from a Colombian population. Multiplex Ligation-Dependent Probe Amplification (MLPA) was performed for the identification of CNVs in 40 genomic regions of 11 CYP-450 and 3 GST genes. The genetic variability, allelic and genotypic frequencies were analyzed. Results: We found that 13 out of 14 genes had CNVs: 5 (35.7%) exhibited deletions and duplications, while 8 (57.1%) presented either deletions or duplications.. 33.3% of individuals carried deletions and duplications while 49.6% had a unique type of CNV (deletion or duplication). The allelic frequencies of the CYP and GST genes were 0 to 47.6% (allele null), 0 to 17.5% (duplicated alleles) and 37 to 100% (normal alleles). Conclusions: Our results describe, for the first time, the genomic profile of CNVs in a subgroup of Colombian population in GST and CYP-450 genes. GST genes indicated greater genetic variability than CYP-450 genes. The data obtained contributes to the knowledge of genetic profiles in Latin American subgroups. Although the clinical relevance of CNVs has not been fully established, it is a valuable source of pharmacogenetic variability data with potential involvement in the response to medications.

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“…A strong recommendation (level A) is expected to be chosen by a majority of informed healthcare providers and patients. A recommendation in the category "Moderate" is expected to require individualized informed decision making by patients and healthcare providers (Ross et al, 2010;Amstutz et al, 2014;Tanoshima et al, 2019).…”

Section: Canadian Pharmacogenomics Network For Drug Safetymentioning

confidence: 99%

“…The DPWG has adopted "normal metabolizer" (NM) for CYP2D6, CYP2C19, CYP3A4, CYP1A2, CYP2B6, TPMT, and NUDT15 (The Dutch Pharmacogenomic Working Group, 2020b). The CPNDS also used "normal metabolizer" in its guideline on tamoxifen (Tanoshima et al, 2019). However, for CYP3A5 the DPWG decided to maintain the phenotype terminology, "CYP3A5 non-expressor," for carriers of two nonfunctional alleles (CYP3A5*3/*3), "CYP3A5 heterozygous-expressor" and "CYP3A5 homozygous-expressor."…”

Section: Terminology Of Predicted Phenotypesmentioning

confidence: 99%

Pharmacogenetics Guidelines: Overview and Comparison of the DPWG, CPIC, CPNDS, and RNPGx Guidelines

et al. 2021

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Many studies have shown that the efficacy and risk of side effects of drug treatment is influenced by genetic variants. Evidence based guidelines are essential for implementing pharmacogenetic knowledge in daily clinical practice to optimize pharmacotherapy of individual patients. A literature search was performed to select committees developing guidelines with recommendations being published in English. The Dutch Pharmacogenetics Working Group (DPWG), the Clinical Pharmacogenetics Implementation Consortium (CPIC), the Canadian Pharmacogenomics Network for Drug Safety (CPNDS), and the French National Network (Réseau) of Pharmacogenetics (RNPGx) were selected. Their guidelines were compared with regard to the methodology of development, translation of genotypes to predicted phenotypes, pharmacotherapeutic recommendations and recommendations on genotyping. A detailed overview of all recommendations for gene-drug combinations is given. The committees have similar methodologies of guideline development. However, the objectives differed at the start of their projects, which have led to unique profiles and strengths of their guidelines. DPWG and CPIC have a main focus on pharmacotherapeutic recommendations for a large number of drugs in combination with a patient’s genotype or predicted phenotype. DPWG, CPNDS and RNPGx also recommend on performing genetic testing in daily clinical practice, with RNPGx even describing specific clinical settings or medical conditions for which genotyping is recommended. Discordances exist, however committees also initiated harmonizing projects. The outcome of a consensus project was to rename “extensive metabolizer (EM)” to “normal metabolizer (NM)”. It was decided to translate a CYP2D6 genotype with one nonfunctional allele (activity score 1.0) into the predicted phenotype of intermediate metabolizer (IM). Differences in recommendations are the result of the methodologies used, such as assessment of dose adjustments of tricyclic antidepressants. In some cases, indication or dose specific recommendations are given for example for clopidogrel, codeine, irinotecan. The following drugs have recommendations on genetic testing with the highest level: abacavir (HLA), clopidogrel (CYP2C19), fluoropyrimidines (DPYD), thiopurines (TPMT), irinotecan (UGT1A1), codeine (CYP2D6), and cisplatin (TPMT). The guidelines cover many drugs and genes, genotypes, or predicted phenotypes. Because of this and their unique features, considering the totality of guidelines are of added value. In conclusion, many evidence based pharmacogenetics guidelines with clear recommendations are available for clinical decision making by healthcare professionals, patients and other stakeholders.

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Analyses of Adverse Drug Reactions–Nationwide Active Surveillance Network: Canadian Pharmacogenomics Network for Drug Safety Database

Cited by 14 publications

References 32 publications

Drug‐Induced Ototoxicity: A Comprehensive Review and Reference Guide

Drug‐Induced Ototoxicity: A Comprehensive Review and Reference Guide

Copy number variation profiling in pharmacogenetics CYP-450 and GST genes in Colombian population

Pharmacogenetics Guidelines: Overview and Comparison of the DPWG, CPIC, CPNDS, and RNPGx Guidelines

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