Abstract
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.
Highlights
The effects of drugs in terms of the beneficial outcomes of drug treatment, development of side effects, and toxicity are influenced by genetic variants
Pharmacogenetics guidelines of the Dutch Pharmacogenetics Working Group (DPWG), Clinical Pharmacogenetics Implementation Consortium (CPIC), Canadian Pharmacogenomics Network for Drug Safety (CPNDS) and RNPGx were found through performing the PubMed search
The DPWG and CPIC guidelines were compared by Bank et al (2018) based on the guidelines published until March 1, 2017
Summary
The effects of drugs in terms of the beneficial outcomes of drug treatment, development of side effects, and toxicity are influenced by genetic variants. Many studies have shown that the pharmacokinetics and effects of drugs differ among patients with specific genetic profiles. Evidence-based guidelines with pharmacotherapeutic recommendations for combinations of specific drugs and genotypes or predicted phenotypes are essential for implementing acquired pharmacogenetics knowledge in daily clinical practice. The Dutch Pharmacogenetics Working Group (DPWG) and the Clinical Pharmacogenetics Implementation Consortium (CPIC) have been developing guidelines for more than a decade (Swen et al, 2008; Swen et al, 2011a; Caudle et al, 2017). Recommendations are preferably made available at the time of drug prescribing and dispensing for a patient with a genotype that requires an action, such as a dose reduction (Swen et al, 2008; Swen et al, 2011a; Deneer and van Schaik, 2013)
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