Clinical Relevant Drug-drug Interactions Research Articles

Drug-drug interactions with direct oral anticoagulants: development of a consensus list for ambulatory care.

Direct oral anticoagulants (DOACs) can be involved in clinical relevant drug-drug interactions (DDIs) which may compromise safe and effective use. However, assessing the clinical relevance of DDIs with DOACs and managing these interactions optimally, can be challenging in clinical practice. To develop a practice-oriented list of potentially clinically relevant DDIs with DOACs with corresponding management plans for which it is important to screen in ambulatory care. The RAND/UCLA appropriateness method was used to develop the DOACs DDI list. In a first step a preliminary list was compiled of potentially clinically relevant DDIs per DOAC (apixaban, dabigatran, edoxaban, rivaroxaban) using five reference sources. Subsequently, a two-step modified Delphi process involving a multidisciplinary panel (n = 10) including both pharmacists and physicians with expertise in all decision-making disciplines involved in care for patients using DOACs and with diversity of practice setting, was used to reach expert agreement on a final list of DDIs with corresponding management plans. After a two-step consensus round, 71 DDIs for 20 different interacting drugs were included: five pharmacodynamic, nine pharmacokinetic inhibitor and six pharmacokinetic inducer interacting drugs. Considerations raised and discussed by the panellists were related to (1) the necessity of the interacting drug, (2) the manageability of the DDI (whether there are any alternatives), (3) the (clinical) evidence-base for the DDI and (4) the (potential) consequences of the DDI. We developed a consensus list with specific and straightforward management plans on potentially clinically relevant DDIs with DOACs, for use in ambulatory care.

Management of clinical relevant drug-drug interactions with antipsychotics in nursing homes

Introduction Antipsychotics (APs) have been linked to several clinically relevant drug-drug interactions (leading, e.g. to QT-prolongation, torsades de pointes) but little is known about their management in nursing homes residents. Our aim was to characterise clinically relevant drug-drug interactions involving APs and to assess their prevalence in nursing homes residents. Materials and methods We conducted a cross-sectional study in two nursing homes in Portugal. Patients were included if they were older ≥65 and prescribed at least one AP (registered in medical charts). Interactions were identified using Drug Interaction Chequer (Medscape [1]) and supplemented with the summary of product characteristics (SmPC) when deemed necessary. Clinical relevant interactions were defined as serious or contraindicated interactions according to Medscape tool. Data were analysed using univariate statistics (Microsoft Excel 2016). Results A total of 59 patients (83.7 ± 7.1 years) were analysed, 79.7% (n = 47) females. A mean of 1.6 ± 0.7 antipsychotics were prescribed/patient, mostly on a regular basis (61.0%; n = 36). The majority were exclusively prescribed atypical APs (59.3%; n = 35), 28.8% (n = 17) simultaneously atypical and typical APs and 11.9% (n = 7) prescribed only typical APs. Nearly 90% (n = 52; 88.1%) of patients reported interactions with APs, (mean = 2.9 ± 2.3/patient). A total of 169 interactions with APs were found, mainly with antidepressants (27.2%; n = 46), benzodiazepines (22.4%; n = 38), and other antipsychotics (10.6%; n = 18). The majority of AP-drug interactions (83.4%; n = 141) were classified as “to be closely monitored”, mostly due to the sedation effect (56.7%; n = 80). Quetiapine was the AP most often involved in interactions (45.6%; n = 77), where 9.1% (n = 7) were considered “serious”. Haloperidol also registered 37 interactions (21.9%), four of which resulted in increased QTc interval (10.8%). Discussion and conclusions Data showed that one third of patients had clinically relevant AP-drug interactions. Future work will include the development of a user-friendly booklet on clinical relevant drug-drug interactions in elderly patients using APs, expected to contribute to enhanced patient safety and a more rational use of medicines.

Role of OATP1B1 and OATP1B3 in Drug-Drug Interactions Mediated by Tyrosine Kinase Inhibitors.

Failure to recognize important features of a drug’s pharmacokinetic characteristics is a key cause of inappropriate dose and schedule selection, and can lead to reduced efficacy and increased rate of adverse drug reactions requiring medical intervention. As oral chemotherapeutic agents, tyrosine kinase inhibitors (TKIs) are particularly prone to cause drug-drug interactions as many drugs in this class are known or suspected to potently inhibit the hepatic uptake transporters OATP1B1 and OATP1B3. In this article, we provide a comprehensive overview of the published literature and publicly-available regulatory documents in this rapidly emerging field. Our findings indicate that, while many TKIs can potentially inhibit the function of OATP1B1 and/or OATP1B3 and cause clinically-relevant drug-drug interactions, there are many inconsistencies between regulatory documents and the published literature. Potential explanations for these discrepant observations are provided in order to assist prescribing clinicians in designing safe and effective polypharmacy regimens, and to provide researchers with insights into refining experimental strategies to further predict and define the translational significance of TKI-mediated drug-drug interactions.

Polypharmacy, potentially serious clinically relevant drug-drug interactions, and inappropriate medicines in elderly people with type 2 diabetes and their impact on quality of life.

The aim of the study is to investigate the patterns of polypharmacy, clinical‐relevant drug‐drug interactions (DDIs), and potentially inappropriate medicines (PIMs), and whether polypharmacy, potential serious clinically‐relevant DDIs, or PIMs can be associated with low quality of life (QoL) index scores of older adults with type 2 diabetes (T2D). A cross‐sectional study was conducted using data of 670 elderly T2D sub‐cohort from a nationwide pharmacy‐based intensive monitoring study of inception cohort of T2D in Portugal. 72.09% were found on polypharmacy (≥5 medicines). Participants on polypharmacy were mostly females (P = .0115); more obese (P = .0131); have more comorbid conditions (P < .0001); more diabetes complications (P < .0001); and use more of glucose lowering drugs (P = .0326); insulin (P < .0001); chronic medicines (P < .0001); and have higher diabetes duration (P = .0088) than those without polypharmacy. 10.59% of the participants were found to have potential serious clinically relevant DDIs. The most frequent drug‐combinations were angiotensin‐converting enzyme (ACE) inhibitors with angiotensin‐receptor blockers (ARBs), aspirin with Selective serotonin reuptake inhibitors (SSRIs), and clopidogrel with calcium channel blockers. PIMs are found in 36.11% of the participants. The most common PIMs were benzodiazepines, long‐acting sulfonylureas, and iron overdose. The adjusted multivariate models show that Polypharmacy, PIMs, and potential serious clinically relevant DDIs were associated with lower QoL index scores (OR 1.80 95% CI 1.15‐2.82), (OR 1.57 95% CI 1.07‐2.28), and (OR 1.34 95% CI 0.73‐2.48) respectively. The study shows that polypharmacy, potential serious clinical‐relevant DDIs, and PIMs may correlate with risk of reduced health related QoL outcome of older adults with T2D.

Potential and clinical relevant drug-drug interactions among elderly from nursing homes: a multicentre study in Murcia, Spain

This study purposes to determine the prevalence of potential and clinical relevant Drug-Drug-Interactions (pDDIs) in institutionalized older adults and to identify the pertinent factors associated. We conduct an observational, multicenter and cross-sectional study during the last quarter of 2010. We selected a sample of 275 subjects (aged ≥ 65 years) from 10 nursing homes of Murcia (Spain) by a two-stage complex sampling. pDDIs were identified using the College of Pharmacists Database. We only considered pDDIs of clinical relevance, and thereafter the relevant factors were identified through uni-level and multi-level regression analyses. A total of 210 pDDIs were identified, 120 of which were considered clinically relevant (57.1%), affecting a total of 70 elderly (25.8%). Eight pharmacological groups made up 70.2% of the clinically relevant pDDIs. More clinically relevant DDIs were found in people suffering several pathologies (OR = 2.3; 95%CI = 1.4-4.5), and also in people who take ten or more drugs daily (OR = 9.6; 95%CI = 4.8-19.1), and people who take anti-inflammatory drugs (OR = 3.9; 95%CI = 1.4-10.4). This study reveals that clinically relevant pDDIs are very common in institutionalized elderly people, and that caregivers should aim at improving their practice in order to reduce the prevalence of this phenomenon.

Micropatterned Co‐Cultures of Human Hepatocytes and Stromal Cells for the Assessment of Drug Clearance and Drug‐Drug Interactions

Drug clearance rates from the body can determine drug exposure that can affect efficacy or toxicity. Thus, accurate prediction of drug clearance during preclinical development can help guide dose selection in humans, but animal testing is not always predictive of human outcomes. Because hepatic drug metabolism is a rate-limiting step in the overall clearance of many drugs, primary human hepatocytes (PHHs) in suspension cultures or monolayers are used for drug clearance predictions. Yet, the precipitous decline in drug metabolism capacity can lead to significant underestimation of clearance rates, particularly for low turnover compounds that have desirable one-pill-a-day dosing regimens. In contrast, micropatterned co-cultures (MPCCs) of PHHs and fibroblasts display phenotypic stability for several weeks and can help mitigate the limitations of conventional cultures. Here, we describe protocols to create and use MPCCs for drug clearance predictions, and for modeling clinically-relevant drug-drug interactions that can affect drug clearance. © 2017 by John Wiley & Sons, Inc.

Use of Psychotropics and Drug-Drug Interactions in Oncology: Reflections from a Study in a Portuguese Psycho-Oncology Unit

Introduction: Psychopharmacological treatment is an important tool of the multidimensional approach in oncologic setting but cancer patient´s susceptibility to drug-drug interactions may pose them at risk. Objective: To describe the use of psychotropic in patients referred to a psycho-oncology unit and to point out potential and clinical relevant drug-drug interactions in this context. Methods: Descriptive study of a sample of patients referred for the first time to the Psycho-Oncology Unit of Coimbra University Hospital Centre, between April and December 2013. A retrospective collection of the sociodemographic, clinical and prescription data was made by consulting clinical processes. Results: From the sample of 110 patients, 51,8% of the patients were already taking some psychotropic drug and 91,9% were on antineoplastic medication at the time of the psycho-oncology appointment. Among the psychotropic medication, almost all were benzodiazepines and antidepressants. Psychotropic can cause potential interactions with antineoplastic medication administered in cancer patients. Some pharmacological agents have more potential to cause drug-drug interactions. Conclusions: Prescription of psychotropic medication by the oncological team is common and cancer patients usually take several drugs at the same time. This study outlines the importance of promoting scientific research on drug-drug interactions in psycho-oncology and a closer collaboration between oncology and psychiatry in order to reduce the risk of drug-drug Interactions, to increase its awareness and to adequately prescribe a psychopharmacologic treatment for each patient.

Micafungin: A brief review of pharmacology, safety, and antifungal efficacy in pediatric patients

Invasive fungal infections are a major cause of morbidity and mortality in children with hematological malignancies and those undergoing allogeneic hematopoietic stem-cell transplantation (HSCT). Although several new antifungal compounds recently became available, some are not yet approved for the use in the pediatric population. Among the new class of echinocandins, micafungin has been licensed in Europe and Japan for children including neonates. Because micafungin is well tolerated and exhibits few clinical relevant drug-drug interactions, the compound is of particular interest for prophylaxis and treatment of invasive mycoses in pediatric patients with cancer or following allogeneic HSCT. This review will focus on the currently available pediatric data of micafungin with emphasis on pharmacokinetics, efficacy, and safety.