Evaluation of Drug—Drug Interactions in EGFR-Mutated Non-Small-Cell Lung Cancer Patients during Treatment with Tyrosine-Kinase Inhibitors

Occhipinti, Mario; Brambilla, Marta; Galli, Giulia; Manglaviti, Sara; Giammaruco, Maristella; Prelaj, Arsela; Ferrara, Roberto; Toma, Alessandro De; Proto, Claudia; Beninato, Teresa; Zattarin, Emma; Russo, Giuseppe Lo; Simmaco, Maurizio; Preißner, Robert; Garassino, Marina Chiara; Braud, Filippo de; Marchetti, Paolo

doi:10.3390/jpm11050424

Cited by 9 publications

(8 citation statements)

References 37 publications

(53 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Drug-PIN® (Personalized Interactions Network) is a medical software able to evaluate clinical, biochemical and demographic patients' data and combine them with a simultaneous DDIs pro le, exploring possible effects also between active and/or pro-drug forms. [21][22][23] Moreover, the software combines and analyses the clinical data (age, weight, liver and renal function), the DDIs, and, if available, the genomic pro le of patients. The output of Drug-PIN system is a numerical score (Drug-PIN score) that indicates the risk of DDIs, and a tier (Drug-PIN tier: green, yellow, dark yellow and red), which indicates how high is the risk of interactions and if the concomitant drugs have to be changed, in a drug reconciliation process.…”

Section: Methodsmentioning

confidence: 99%

Real-world experience and clinical impact of drug-drug interactions in HR+/HER2- advanced breast cancer patients treated with abemaciclib plus endocrine therapy: the AB-ITALY study

Pisegna

Scagnoli

Toss

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

BACKGROUND Abemaciclib demonstrated clinical benefit in women affected by HR+/HER2- advanced breast cancer (aBC). Drug-drug interactions (DDIs) can lead to a reduced treatment efficacy or increased toxicity. This retro-prospective study aimed to evaluate outcomes, DDIs’ impact and toxicities of abemaciclib combined with endocrine therapy in a real-world setting. METHODS Patients from 12 referral Italian hospitals with HR+/HER2- aBC who received abemaciclib were included. Clinical data about comorbidities, concurrent medications, outcomes and adverse events (AE) were collected. Drug-PIN® (Personalized Interactions Network) is a tool recognizing the role of multiple interactions between active and/or pro-drug forms combined with biochemical and demographic patient data. The software was used to define the Drug-PIN score and Drug-PIN tier (green, yellow, dark yellow and red) for each patient. Univariate and multivariate analysis were performed to identify predictors of patients PFS or toxicity. RESULTS One hundred seventy-three patients were included. 13% of patients had > 75years. Overall response rate (ORR) was 63%. The median PFS (mPFS) of the overall population was 22 months (mo), while mOS was not reached. Patients treated with abemaciclib in combination with AI and fulvestrant had a mPFS of 36 and 19 mo, respectively. The most common toxicities were diarrhoea, asthenia and neutropenia detected in 63%,49%,49% of patients, respectively. The number of concomitant medications and comorbidities were not associated with survival outcomes (22 vs 17 mo, p = 0.068, p = 0.99). Drug-PIN tier from dark yellow to red and Drug-PIN score > 12 were associated with shorter PFS compared to no/low risk DDIs and score < 12 (15 vs 23, p = 0.005, p = 0.0017). Drug interaction was confirmed as an independent biomarker in a multivariate model (p = 0.02). No difference in any-grade AE, severe toxicities and diarrhoea was detected among different age subgroups. No association was found between Drug-PIN score or Drug-PIN tier and overall toxicity (p = 0.44), severe AEs (p = 0.11) or drug reduction (p = 0.27) CONCLUSIONS Efficacy and safety of abemaciclib plus ET were confirmed in a real-world setting, even in elderly population and patients with comorbidities. Evaluation of DDIs with Drug-PIN appear to be an independent predictor of PFS.

show abstract

Section: Methodsmentioning

confidence: 99%

Real-world experience and clinical impact of drug-drug interactions in HR+/HER2- advanced breast cancer patients treated with abemaciclib plus endocrine therapy: the AB-ITALY study

Pisegna

Scagnoli

Toss

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Based on the score, drugs can be categorized into three groups: “usable”, “non-preferable” and “not recommended”. 4 , 13 …”

Section: Methodsmentioning

confidence: 99%

“… 8–11 Furthermore, studies in which DDGIs as well as further traits and lifestyle habits of an individual patient have been investigated are rare and again only consider specific drug classes or diseases. 4 , 12 , 13 …”

Section: Introductionmentioning

confidence: 99%

“…[8][9][10][11] Furthermore, studies in which DDGIs as well as further traits and lifestyle habits of an individual patient have been investigated are rare and again only consider specific drug classes or diseases. 4,12,13 This study aimed to establish a prescription ranking for drugs of commonly used drug classes, based on data of patients for which a DDGI profile was generated using the medication support software. This ranking should assist practitioners in their choice of the right drug(s) for those patients for whom no individual DDGI profile exists in order to minimize the risk of ADRs or inefficient therapies.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Prescription Advice Based on Data of Drug-Drug-Gene Interaction of Patients with Polypharmacy

Salamone¹,

Spirito²,

Simmaco³

et al. 2022

PGPM

Self Cite

View full text Add to dashboard Cite

Purpose Pharmacogenetic counselling is a complex task and requires the efforts of an interdisciplinary team, which cannot be implemented in most cases. Therefore, simple rules could help to minimize the risk of medications incompatible with each other or with frequent genetic variants. Patients and Methods One hundred and eighty-four multi-morbid Caucasian patients suffering from side effects or inefficient therapy were enrolled and genotyped. Their medication was analyzed by a team of specialists using Drug-PIN ® (medication support system) and individual recommendations for 34 drug classes were generated. Results In each of the critical drug classes, 50% of the drugs cannot be recommended to be prescribed in typical drug cocktails. PPIs and SSRI/SNRIs represent the most critical drug classes without showing a single favorable drug. Among the well-tolerated drugs (not recommended for less than 5% of the patients) are metamizole, celecoxib, olmesartan and famotidine. For each drug class, a ranking of active ingredients according to their suitability is presented. Conclusion Genotyping and its profound analysis are not available in many settings today. The consideration of frequent alterations of metabolic elimination routes and drug–drug–gene interactions by using simple rankings can help to avoid many incompatibilities, side effects and inefficient therapies.

show abstract

“…The drug-drug interaction risk was analyzed using the INTERCheck® software and the Drug-PIN® (Personalized Interactions Network) tool. By using the INTERCheck® computerized support, the potential DDIs according to their clinical relevance are divided in contraindicated (class D, drug combinations that should be avoided); major (C, drug combinations that need close monitoring for potentially serious clinical consequences); moderate (B, drug combinations requiring dose adjustment); and minor (A, drug combinations with no known clinical relevance) [ 16 ]. The INTERCheck® total score was the sum of all obtained interactions.…”

Section: Methodsmentioning

confidence: 99%

Comparison of Computerized Prescription Support Systems in COVID-19 Patients: INTERCheck and Drug-PIN

Martocchia

Bruscia

Conforti

et al. 2021

SN Compr. Clin. Med.

Self Cite

View full text Add to dashboard Cite

The coronavirus disease 19 (COVID-19) infection requires major efforts in healthcare systems, due to the high risk of mortality, particularly in subjects with significant comorbidity (≥ 2 pathologies) and polypharmacy (≥ 5 drugs). The treatment of COVID-19 needs a careful evaluation, to reduce the risk of potentially adverse drug reactions. The aim of the study was to examine the use of computerized prescription support in the management and treatment of the COVID-19 infection. We evaluated n.33 patients (51% females) admitted to the west COVID Low-Medium Intensity of Care of Sant’Andrea Hospital during the period March–April 2020 and n.42 subjects (50% females) admitted to the Internal Medicine ward (as control group), by INTERCheck® and Drug-PIN®. The comorbidity (n. pathologies), polypharmacy (n. drugs), and total INTERCheck score in COVID-19 patients and controls were, respectively (mean ± standard deviation): 5.8 ± 3.8, 7.9 ± 4.5, and 9.2 ± 7.1 and 6.8 ± 2.6, 8.0 ± 2.6, and 4.9 ± 3.8 (statistically significant for comorbidity p < 0.01 and INTERCheck score p < 0.01). The correlation between the scores obtained by the INTERCheck and Drug-PIN software was statistically significant, either at admission ( p < 0.0000001) or during hospitalization ( p < 0.00000001). Both the computerized prescription support systems, INTERCheck® and Drug-PIN®, are useful to better characterize the patients and to ameliorate the drugs prescriptions in COVID-19 infection, with particular attention to the elderly population.

show abstract

Evaluation of Drug—Drug Interactions in EGFR-Mutated Non-Small-Cell Lung Cancer Patients during Treatment with Tyrosine-Kinase Inhibitors

Cited by 9 publications

References 37 publications

Real-world experience and clinical impact of drug-drug interactions in HR+/HER2- advanced breast cancer patients treated with abemaciclib plus endocrine therapy: the AB-ITALY study

Real-world experience and clinical impact of drug-drug interactions in HR+/HER2- advanced breast cancer patients treated with abemaciclib plus endocrine therapy: the AB-ITALY study

Prescription Advice Based on Data of Drug-Drug-Gene Interaction of Patients with Polypharmacy

Comparison of Computerized Prescription Support Systems in COVID-19 Patients: INTERCheck and Drug-PIN

Contact Info

Product

Resources

About