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Impact of Drug-Gene-Interaction, Drug-Drug-Interaction, and Drug-Drug-Gene-Interaction on (es)Citalopram Therapy: The PharmLines Initiative.

ABSTRACT: We explored the association between CYP2C19/3A4 mediated drug-gene-interaction (DGI), drug-drug-interaction (DDI) and drug-drug-gene-interaction (DDGI) and (es)citalopram dispensing course. A cohort study was conducted among adult Caucasians from the Lifelines cohort (167,729 participants) and linked dispensing data from the IADB.nl database as part of the PharmLines Initiative. Exposure groups were categorized into (es)citalopram starters with DGI, DDI and DDGI. The primary outcome was drug switching and/or dose adjustment, and the secondary was early discontinuation after the start of (es)citalopram. Logistic regression modeling was applied to estimate adjusted odd ratios with their confidence interval. We identified 316 (es)citalopram starters with complete CYP2C19/3A4 genetic information. The CYP2C19 IM/PM and CYP3A4 NM combination increased risks of switching and/or dose reduction (OR: 2.75, 95% CI: 1.03-7.29). The higher effect size was achieved by the CYP2C19 IM/PM and CYP3A4 IM combination (OR: 4.38, 95% CI: 1.22-15.69). CYP2C19/3A4 mediated DDIs and DDGIs showed trends towards increased risks of switching and/or dose reduction. In conclusion, a DGI involving predicted decreased CYP2C19 function increases the need for (es)citalopram switching and/or dose reduction which might be enhanced by co-presence of predicted decreased CYP3A4 function. For DDI and DDGI, no conclusions can be drawn from the results.

SUBMITTER: Bahar MA

PROVIDER: S-EPMC7720126 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Impact of Drug-Gene-Interaction, Drug-Drug-Interaction, and Drug-Drug-Gene-Interaction on (es)Citalopram Therapy: The PharmLines Initiative.

Bahar Muh Akbar MA Lanting Pauline P Bos Jens H J JHJ Sijmons Rolf H RH Hak Eelko E Wilffert Bob B

Journal of personalized medicine 20201128 4

We explored the association between CYP2C19/3A4 mediated drug-gene-interaction (DGI), drug-drug-interaction (DDI) and drug-drug-gene-interaction (DDGI) and (es)citalopram dispensing course. A cohort study was conducted among adult Caucasians from the Lifelines cohort (167,729 participants) and linked dispensing data from the IADB.nl database as part of the PharmLines Initiative. Exposure groups were categorized into (es)citalopram starters with DGI, DDI and DDGI. The primary outcome was drug swi ...[more]

PMID: 33260705

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Project description:Background and objectiveAegis Sciences Corporation developed a test (InterACT Rx™) that objectively and definitively identifies substances known to interact with drug-drug interaction-prone medications commonly prescribed in the treatment of chronic pain and behavioral health disorders. The objective of this study was to assess the severity of identified drug-drug interactions, the reduction in the frequency and severity of identified drug-drug interactions, and the impact of the test on healthcare utilization.MethodsPatients with chronic pain, behavioral health disorders, or both who had one or more drug-drug interaction tests and one or more drug-drug interactions identified in the study period were included. Drug-drug interaction test results described the number and severity of interactions and detected substances involved in drug-drug interactions. Patients' electronic medical records were obtained to analyze outpatient visits and prescription medications. The cost of outpatient visits was based on the Medicare Physician Fee Schedule. Outcomes were compared between the pre- and post-study index periods to determine the impact of the drug-drug interaction test on patient care.ResultsA total of 262 patients were included. The majority of drug-drug interactions detected (77.9%) at index were of moderate severity. The number of monthly all-cause and pain-related outpatient visits was reduced in the post-index period compared with the pre-index period (0.74-0.54 and 0.69-0.49, respectively). Associated costs were reduced from US$64.92 to US$51.20, and from US$62.42 to US$47.62, (p < 0.0001 for both) for all-cause and pain-related outpatient visits, respectively. Follow-up drug-drug interaction testing for 43 patients revealed that previously reported drug-drug interactions at the index test were no longer identified in the subsequent test for 39.5% of patients.ConclusionsEmploying a definitive test to detect substances whose interactions may cause adverse drug events can enhance a provider's insights, drive clinical decision making, and improve patient outcomes.

Dataset Information

Impact of Drug-Gene-Interaction, Drug-Drug-Interaction, and Drug-Drug-Gene-Interaction on (es)Citalopram Therapy: The PharmLines Initiative.

Publications

Impact of Drug-Gene-Interaction, Drug-Drug-Interaction, and Drug-Drug-Gene-Interaction on (es)Citalopram Therapy: The PharmLines Initiative.

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