Dataset Information

Drug-Drug Interactions and Pharmacogenomic Evaluation in Colorectal Cancer Patients: The New Drug-PIN^® System Comprehensive Approach.

ABSTRACT: Drug-drug interactions (DDIs) can affect both treatment efficacy and toxicity. We used Drug-PIN^® (Personalized Interactions Network) software in colorectal cancer (CRC) patients to evaluate drug-drug-gene interactions (DDGIs), defined as the combination of DDIs and individual genetic polymorphisms. Inclusion criteria were: (i) stage II-IV CRC; (ii) ECOG PS (Performance status sec. Eastern coperative oncology group) ?2; (iii) ?5 concomitant drugs; and (iv) adequate renal, hepatic, and bone marrow function. The Drug-PIN^® system analyzes interactions between active and/or pro-drug forms by integrating biochemical, demographic, and genomic data from 110 SNPs. We selected DDI, DrugPin1, and DrugPin2 scores, resulting from concomitant medication interactions, concomitant medications, and SNP profiles, and DrugPin1 added to chemotherapy drugs, respectively. Thirty-four patients, taking a median of seven concomitant medications, were included. The median DrugPin1 and DrugPin2 scores were 42.6 and 77.7, respectively. In 13 patients, the DrugPin2 score was two-fold higher than the DrugPin1 score, with 7 (54%) of these patients experiencing severe toxicity that required hospitalization. On chi-squared testing for any toxicity, a doubled DrugPin2 score (p = 0.001) was significantly related to G3-G4 toxicity. Drug-PIN^® software may prevent severe adverse events, decrease hospitalizations, and improve survival in cancer patients.

SUBMITTER: Roberto M

PROVIDER: S-EPMC7830292 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Drug-Drug Interactions and Pharmacogenomic Evaluation in Colorectal Cancer Patients: The New Drug-PIN<sup>®</sup> System Comprehensive Approach.

Roberto Michela M Rossi Alessandro A Panebianco Martina M Pomes Leda Marina LM Arrivi Giulia G Ierinò Debora D Simmaco Maurizio M Marchetti Paolo P Mazzuca Federica F

Pharmaceuticals (Basel, Switzerland) 20210115 1

Drug-drug interactions (DDIs) can affect both treatment efficacy and toxicity. We used Drug-PIN<sup>®</sup> (Personalized Interactions Network) software in colorectal cancer (CRC) patients to evaluate drug-drug-gene interactions (DDGIs), defined as the combination of DDIs and individual genetic polymorphisms. Inclusion criteria were: (i) stage II-IV CRC; (ii) ECOG PS (Performance status sec. Eastern coperative oncology group) ≤2; (iii) ≥5 concomitant drugs; and (iv) adequate renal, hepatic, and ...[more]

PMID: 33467633

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Project description:PurposeWhile nirmatrelvir/ritonavir (NMV-r) has been positioned as a first-line treatment for mild to moderate COVID-19, it has multiple and significant drug-drug interactions (DDIs). The use of NMV-r in Japan has been limited compared to the United States. This study aimed to describe the distribution of DDIs with NMV-r and their management in patients with COVID-19 under the control of a management system for the appropriate use of NMV-r.MethodsA retrospective observational study was conducted at a Japanese university hospital. The management system included a flowchart for selecting antivirals and a list for reviewing DDI management, based on the National Institutes of Health guidelines and the guidance of the Japanese Society of Pharmaceutical Health Care and Sciences. Patients with mild to moderate COVID-19 and prescribed NMV-r or molnupiravir (MOV) were included. The primary outcome was DDI management practices, including the selected COVID-19 medications. The secondary outcome included the distribution of DDI classification and the 30-day all-cause mortality.ResultsThis study included 241 patients (median age of 60 years, 112 [46.5%] females), of whom 126 and 115 received NMV-r and MOV, respectively. Of the 241 patients, 145 (60.2%) received concomitant medications that have DDIs with NMV-r. All 30 patients with severe renal impairment or insufficient details on concomitant medications received MOV. Forty-nine patients with concomitant medications required alternative COVID-19 therapy consideration due to DDIs, of whom 42 (85.7%) patients received MOV. Eighty-one patients had concomitant medications requiring temporary adjustment, of whom 44 (54.3%) patients received NMV-r, and 42 of these patients temporarily adjusted these concomitant medications. Five patients with concomitant medications that can continued by monitoring the effects/adverse effects, of whom 4 (80.0%) patients received NMV-r. Seventy-six patients without concomitant medications requiring DDI management, of whom 71 (93.4%) patients received NMV-r. The 30-day all-cause mortality for eligible patients was 0.9% [95% confidence interval, 0.1-3.1].ConclusionsMost patients received appropriate antivirals according to the classification of DDIs, and most patients with concomitant medications requiring temporary adjustment received the recommended DDI management. Our management system is effective in promoting the use of NMV-r in the appropriate patients and managing problematic DDIs.

Dataset Information

Drug-Drug Interactions and Pharmacogenomic Evaluation in Colorectal Cancer Patients: The New Drug-PIN^® System Comprehensive Approach.

Publications

Drug-Drug Interactions and Pharmacogenomic Evaluation in Colorectal Cancer Patients: The New Drug-PIN<sup>®</sup> System Comprehensive Approach.

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OmicsDI is part of the ELIXIR infrastructure

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Dataset Information

Drug-Drug Interactions and Pharmacogenomic Evaluation in Colorectal Cancer Patients: The New Drug-PIN® System Comprehensive Approach.

Publications

Drug-Drug Interactions and Pharmacogenomic Evaluation in Colorectal Cancer Patients: The New Drug-PIN<sup>®</sup> System Comprehensive Approach.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Drug-Drug Interactions and Pharmacogenomic Evaluation in Colorectal Cancer Patients: The New Drug-PIN^® System Comprehensive Approach.