Publications by authors named "E Eliasson"

124 Publications

CYP2D6 genotype predicts tamoxifen discontinuation and drug response: a secondary analysis of the KARISMA trial.

Ann Oncol 2021 Oct 18;32(10):1286-1293. Epub 2021 Jul 18.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Background: Guidelines regarding whether tamoxifen should be prescribed based on women's cytochrome P450 2D6 (CYP2D6) genotypes are conflicting and have caused confusion. This study aims to investigate if CYP2D6 metabolizer status is associated with tamoxifen-related endocrine symptoms, tamoxifen discontinuation, and mammographic density change.

Patients And Methods: We used data from 1440 healthy women who participated the KARISMA dose determination trial. Endocrine symptoms were measured using a modified Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES) questionnaire. Change in mammographic density was measured and used as a proxy for tamoxifen response. Participants were genotyped and categorized as poor, intermediate, normal, or ultrarapid CYP2D6 metabolizers.

Results: The median endoxifen level per mg oral tamoxifen among poor, intermediate, normal and ultrarapid CYP2D6 metabolizers were 0.18 ng/ml, 0.38 ng/ml, 0.56 ng/ml and 0.67 ng/ml, respectively. Ultrarapid CYP2D6 metabolizers were more likely than other groups to report a clinically relevant change in cold sweats, hot flash, mood swings, being irritable, as well as the overall modified FACT-ES score, after taking tamoxifen. The 6-month tamoxifen discontinuation rates among poor, intermediate, normal, and ultrarapid CYP2D6 metabolizers were 25.7%, 23.6%, 28.6%, and 44.4%, respectively. Among those who continued and finished the 6-month tamoxifen intervention, the mean change in dense area among poor, intermediate, normal, and ultrarapid CYP2D6 metabolizers were -0.8 cm, -4.5 cm, -4.1 cm, and -8.0 cm respectively.

Conclusions: Poor CYP2D6 metabolizers are likely to experience an impaired response to tamoxifen, measured through mammographic density reduction. In contrast, ultrarapid CYP2D6 metabolizers are at risk for exaggerated response with pronounced adverse effects that may lead to treatment discontinuation.
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http://dx.doi.org/10.1016/j.annonc.2021.07.005DOI Listing
October 2021

[Pharmacogenomics - a cornerstone of Precision Medicine. Genomic Medicine Sweden analyses genotypes associated with serious drug toxicity or therapeutic failure].

Lakartidningen 2021 05 11;118. Epub 2021 May 11.

professor, överläkare, Klinisk farmakologi, Uppsala universitet; Akademiska laboratoriet, Uppsala; båda för arbetsgruppen för farmakogenomik, Genomic Medicine Sweden.

Serious adverse drug reactions, drug intolerance, and lack of effect are major problems in healthcare. Pharmacogenomics is the part of precision medicine that aims to develop predictive risk markers in this respect and establish such testing in clinical practice. The nation-wide project Genomic Medicine Sweden (GMS) is undertaking large-scale sequencing to predict risk of drug toxicity and lack of efficacy in malignant diseases. The aim is to facilitate an improved, individualized treatment with increased patient safety. In addition to accurate genotyping, other technical or infrastructure-related aspects need to be considered for a successful implementation in healthcare, for example electronic accessibility and visibility of pharmacogenomic data of long-standing relevance for an individual's ongoing and future drug treatment.
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May 2021

Poor Correlation between Meropenem and Piperacillin Plasma Concentrations and Delivered Dose of Continuous Renal Replacement Therapy.

Antimicrob Agents Chemother 2021 03 18;65(4). Epub 2021 Mar 18.

Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.

There is insufficient data on the relationship between antibiotic dosing and plasma concentrations in patients treated with continuous renal replacement therapy (CRRT). In this prospective observational study, we explored the variability in plasma concentrations of meropenem and piperacillin in critically ill patients treated with CRRT and the correlation between concentrations and CRRT intensity. Antibiotic concentrations were measured at the middle and end of the dosing interval and repeated after 2 to 3 days when feasible. Measured concentrations were compared to the clinical susceptible breakpoints for , 16 and 2 mg/liter for piperacillin and meropenem, respectively. CRRT intensity was estimated by delivered, time-averaged, total effluent flow ( ), corrected for predilution. Concentrations were also compared between patients with different residual diuresis. We included 140 meropenem concentrations from 98 patients and 47 piperacillin concentrations from 37 patients. Concentrations at the middle of the dosing interval were above target at all occasions for both antibiotics. For meropenem, 6.5% of trough concentrations were below target, and for piperacillin, 22%. Correlations between and antibiotic concentrations or the concentration half-life ( ) were either statistically not significant or weak. Meropenem concentrations and values differed between patients with different residual diuresis. Thus, when treating intensive care patients with CRRT and recommended doses of meropenem or piperacillin, both low, suboptimal plasma concentrations and unnecessarily high, potentially toxic, plasma concentrations are common. Plasma concentrations cannot be predicted from CRRT intensity. Residual diuresis is associated with lower meropenem concentrations, but the correlation is weak. Concentration measurement is probably the most useful approach to avoid suboptimal treatment.
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http://dx.doi.org/10.1128/AAC.02029-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097483PMC
March 2021
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