Pharmacogenetic information in Swiss drug labels – a systematic analysis

Jeiziner, Chiara; Suter, Katja; Wernli, Ursina; Barbarino, Julia M.; Gong, Li; Whirl‐Carrillo, Michelle; Klein, Teri E.; Szucs, Thomas D.; Hersberger, Kurt E.; Schwabedissen, Henriette E. Meyer zu

doi:10.1038/s41397-020-00195-4

Cited by 17 publications

(16 citation statements)

References 44 publications

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“…12 Over the years, PharmGKB annotations of drug labels have expanded and we now curate labels containing PGx information from the European Medicines Agency and Health Canada (HCSC) as these labels come to our attention. We have also partnered with collaborators in one‐off projects to curate labels from Swissmedic 13 and Japan’s Pharmaceuticals and Medical Devices Agency (PMDA).…”

mentioning

confidence: 99%

An Evidence‐Based Framework for Evaluating Pharmacogenomics Knowledge for Personalized Medicine

Whirl‐Carrillo

Huddart

Gong

et al. 2021

Clin Pharma and Therapeutics

427

303

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Clinical annotations are one of the most popular resources available on the Pharmacogenomics Knowledgebase (PharmGKB). Each clinical annotation summarizes the association between variant‐drug pairs, shows relevant findings from the curated literature, and is assigned a level of evidence (LOE) to indicate the strength of support for that association. Evidence from the pharmacogenomic literature is curated into PharmGKB as variant annotations, which can be used to create new clinical annotations or added to existing clinical annotations. This means that the same clinical annotation can be worked on by multiple curators over time. As more evidence is curated into PharmGKB, the task of maintaining consistency when assessing all the available evidence and assigning an LOE becomes increasingly difficult. To remedy this, a scoring system has been developed to automate LOE assignment to clinical annotations. Variant annotations are scored according to certain attributes, including study size, reported P value, and whether the variant annotation supports or fails to find an association. Clinical guidelines or US Food and Drug Administration (FDA)‐approved drug labels which give variant‐specific prescribing guidance are also scored. The scores of all annotations attached to a clinical annotation are summed together to give a total score for the clinical annotation, which is used to calculate an LOE. Overall, the system increases transparency, consistency, and reproducibility in LOE assignment to clinical annotations. In combination with increased standardization of how clinical annotations are written, use of this scoring system helps to ensure that PharmGKB clinical annotations continue to be a robust source of pharmacogenomic information.

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mentioning

confidence: 99%

An Evidence‐Based Framework for Evaluating Pharmacogenomics Knowledge for Personalized Medicine

Whirl‐Carrillo

Huddart

Gong

et al. 2021

Clin Pharma and Therapeutics

427

303

View full text Add to dashboard Cite

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“…Reduced endoxifen concentrations and thus reduced efficacy can also be expected in so-called poor metabolizers for CYP2D6 (see ‘Pharmacokinetics’ and ‘Properties/Effects’). 14 This information is similar to the drug label issued by the FDA and Health Canada. 15 Finally, the National Comprehensive Cancer Network (NCCN) Breast Cancer Panel does not recommend CYP2D6 genotyping.…”

Section: Discussion and Decision-makingmentioning

confidence: 82%

Enriching Medication Review with a Pharmacogenetic Profile – A Case of Tamoxifen Adverse Drug Reactions

Jeiziner¹,

Stäuble²,

Lampert³

et al. 2021

PGPM

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Pharmacogenotyping is applied to determine the hereditable component of a patient's susceptibility to experience therapy failure and/or adverse drug reactions (ADRs). We present the case of a female patient diagnosed with breast cancer and treated with tamoxifen as recurrence therapy who experienced various ADRs. Pharmacogenotyping revealed variants in the cytochrome P450 (CYP) enzymes CYP2D6, CYP2C9, and CYP2C19. The observed genotype was associated with a risk for lower tamoxifen efficacy. Aside from the tamoxifen therapy, the comedication was reviewed for the influence of the patient’s pharmacogenetic profile. As a result of this pharmacist-led medication review with pharmacogenetic analyses, concrete genotype-driven recommendations for the treating gynecologist were compiled. This case revealed the added value of a large pharmacogenetic panel and the complexity of integrating a pharmacogenetic profile into a recommendation.

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“…In the case of several antipsychotics, namely, aripiprazole, haloperidol, risperidone, and zuclopenthixol, a gene–drug interaction with CYP2D6 has been rated as actionable, meaning that there is clinical evidence for dose adaptation to the respective geno- or phenotype. Accordingly, to prevent toxicities, a dose reduction is recommended for patients with predicted reduced CYP2D6 activity [ 5 ], and drug labels draw attention to possible risks [ 6 ]. Currently, no such pharmacogenetic recommendations are available for the widely prescribed atypical antipsychotic quetiapine.…”

Section: Introductionmentioning

confidence: 99%

Severe Adverse Drug Reactions to Quetiapine in Two Patients Carrying CYP2D6*4 Variants: A Case Report

Stäuble

Lampert

Mikoteit

et al. 2021

IJMS

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We report two cases of patients who developed severe adverse drug reactions including persistent movement disorders, nausea, and vertigo during treatment with quetiapine at maximum daily doses ranging between 300 and 400 mg. The extensive hepatic metabolism of quetiapine is mainly attributed to cytochrome P450 3A4 (CYP3A4). However, there is recent evidence supporting the idea of CYP2D6 playing a role in the clearance of the quetiapine active metabolite norquetiapine. Interestingly, both patients we are reporting of are carriers of the CYP2D6*4 variant, predicting an intermediate metabolizer phenotype. Additionally, co-medication with a known CYP2D6 inhibitor and renal impairment might have further affected quetiapine pharmacokinetics. The herein reported cases could spark a discussion on the potential impact of a patient’s pharmacogenetic predisposition in the treatment with quetiapine. However, further studies are warranted to promote the adoption of pharmacogenetic testing for the prevention of drug-induced toxicities associated with quetiapine.

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Pharmacogenetic information in Swiss drug labels – a systematic analysis

Cited by 17 publications

References 44 publications

An Evidence‐Based Framework for Evaluating Pharmacogenomics Knowledge for Personalized Medicine

An Evidence‐Based Framework for Evaluating Pharmacogenomics Knowledge for Personalized Medicine

Enriching Medication Review with a Pharmacogenetic Profile – A Case of Tamoxifen Adverse Drug Reactions

Severe Adverse Drug Reactions to Quetiapine in Two Patients Carrying CYP2D6*4 Variants: A Case Report

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