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

Jeiziner, Chiara; Stäuble, Céline K; Lampert, Markus L.; Hersberger, Kurt E.; Schwabedissen, Henriette E. Meyer zu

doi:10.2147/pgpm.s285807

Cited by 4 publications

(3 citation statements)

References 38 publications

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“…At present, the impact of CYP2D6 and its genetic variants on overall quetiapine and, especially, norquetiapine clearance is still not well elucidated, and further research is needed to allow a recommendation for its management in clinical practice. On the one hand, cases like these, including our recently reported cases on antidepressants and tamoxifen [ 26 , 27 ], point out the complexity and the yet still fragmentary available evidence, making the integration of pharmacogenetic data into clinical practice challenging. On the other hand, the consideration of pharmacogenetic predispositions may offer additional insights for a better understanding of adverse drug reactions as well as of non-response and create an opportunity for healthcare professionals to further enhance safety and effectiveness of marketed drugs.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…Following the referral by the treating physician, the recruited patients underwent the process, as depicted in Figure 1 . Individual cases from the series were published as case reports [ 21 , 22 , 23 , 24 , 25 , 26 ]. The work experience that was gathered within the observational case series study was used to further refine the PGx service over the duration of 3 years between 2019 and 2021, and was based on feedback from patients and treating physicians that was further elaborated in a mixed methods study [ 27 ].…”

Section: Methodsmentioning

confidence: 99%

A Guide to a Pharmacist-Led Pharmacogenetic Testing and Counselling Service in an Interprofessional Healthcare Setting

et al. 2022

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Genetic predisposition is one factor influencing interindividual drug response. Pharmacogenetic information can be used to guide the selection and dosing of certain drugs. However, the implementation of pharmacogenetics (PGx) in clinical practice remains challenging. Defining a formal structure, as well as concrete procedures and clearly defined responsibilities, may facilitate and increase the use of PGx in clinical practice. Over 140 patient cases from an observational study in Switzerland formed the basis for the design and refinement of a pharmacist-led pharmacogenetics testing and counselling service (PGx service) in an interprofessional setting. Herein, we defined a six-step approach, including: (1) patient referral; (2) pre-test-counselling; (3) PGx testing; (4) medication review; (5) counselling; (6) follow-up. The six-step approach supports the importance of an interprofessional collaboration and the role of pharmacists in PGx testing and counselling across healthcare settings.

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“…7 This study was designed to compile case reports to acquire experience with the application of PGx in Swiss primary and secondary care as a basis for the implementation of a standard of procedure. After three years of collecting those patient cases and publishing selected individual case reports, [14][15][16][17][18][19] we aimed to perform a database analysis of all gathered data of the study population.…”

Section: Introductionmentioning

confidence: 99%

Genotyping of Patients with Adverse Drug Reaction or Therapy Failure: Database Analysis of a Pharmacogenetics Case Series Study

Bollinger¹,

Stäuble²,

Jeiziner³

et al. 2023

PGPM

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Pharmacogenetics (PGx) is an emerging aspect of personalized medicine with the potential to increase efficacy and safety of pharmacotherapy. However, PGx testing is still not routinely integrated into clinical practice. We conducted an observational case series study where PGx information from a commercially available panel test covering 30 genes was integrated into medication reviews. The aim of the study was to identify the drugs that are most frequently object of drug-gene-interactions (DGI) in the study population. Patients and Methods:In out-patient and in-patient settings, we recruited 142 patients experiencing adverse drug reaction (ADR) and/or therapy failure (TF). Collected anonymized data from the individual patient was harmonized and transferred to a structured database. Results:The majority of the patients had a main diagnosis of a mental or behavioral disorder (ICD-10: F, 61%), of musculoskeletal system and connective tissue diseases (ICD-10: M, 21%), and of the circulatory system (ICD-10: I, 11%). The number of prescribed medicines reached a median of 7 per person, resulting in a majority of patients with polypharmacy (≥5 prescribed medicines, 65%). In total, 559 suspected DGI were identified in 142 patients. After genetic testing, an association with at least one genetic variation was confirmed for 324 suspected DGI (58%) caused by 64 different drugs and 21 different genes in 141 patients. After 6 months, PGxbased medication adjustments were recorded for 62% of the study population, whereby differences were identified in subgroups. Conclusion:The data analysis from this study provides valuable insights for the main focus of further research in the context of PGx. The results indicate that most of the selected patients in our sample represent suitable target groups for PGx panel testing in clinical practice, notably those taking drugs for mental or behavioral disorder, circulatory diseases, immunological diseases, pain-related diseases, and patients experiencing polypharmacy.

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

Cited by 4 publications

References 38 publications

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

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

A Guide to a Pharmacist-Led Pharmacogenetic Testing and Counselling Service in an Interprofessional Healthcare Setting

Genotyping of Patients with Adverse Drug Reaction or Therapy Failure: Database Analysis of a Pharmacogenetics Case Series Study

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