Drug-drug interactions with tyrosine-kinase inhibitors:A clinical perspective

In the past decade, many tyrosine-kinase inhibitors have been introduced in oncology and haemato-oncology. Because this new class of drugs is extensively used, serious drug-drug interactions are an increasing risk. In this Review, we give a comprehensive overview of known or suspected drug-drug interactions between tyrosine-kinase inhibitors and other drugs. We discuss all haemato-oncological and oncological tyrosine-kinase inhibitors that had been approved by Aug 1, 2013, by the US Food and Drug Administration or the European Medicines Agency. Various clinically relevant drug interactions with tyrosine-kinase inhibitors have been identified. Most interactions concern altered bioavailability due to altered stomach pH, metabolism by cytochrome P450 isoenzymes, and prolongation of the QTc interval. To guarantee the safe use of tyrosine-kinase inhibitors, a drugs review for each patient is needed. This Review provides specific recommendations to guide haemato-oncologists, oncologists, and clinical pharmacists, through the process of managing drug-drug interactions during treatment with tyrosine-kinase inhibitors in daily clinical practice

Evidence- and consensus-based guidelines for drug-drug interactions with anticancer drugs:A practical and universal tool for management

Drug-drug interactions (DDIs) with anticancer drugs are common and can significantly affect efficacy and toxicity of treatment. Therefore, a Dutch Multidisciplinary Expert group is assessing the clinical signifi-cance of DDIs in oncology and provides recommendations for the management of these DDIs. We present an overview of methodology and outcome of an evidence-and consensus-based assessment of DDIs be-tween anticancer drugs and non-anticancer drugs.A literature search was performed through PubMed and EMA and FDA assessment reports, to iden-tify potential DDI's involving anticancer drugs. For each potential DDI a concept report for risk analysis and practical advice for management was created. Subsequently, this risk analysis and the corresponding advice were assessed and weighed.A total of 290 potential DDIs have been identified in the literature thus far. Of these 290 potential DDIs, the Expert Group has identified 94 (32%) DDIs as clinically relevant, with a need for an automated alert and a suggested intervention. Furthermore, 110 DDIs have been identified as clinically not relevant. For 86 potential DDIs evidence supporting a relevant DDI was insufficient and in these cases neither an alert nor advice regarding a suggested intervention were formulated.A transparent risk analysis is presented for identification of clinically relevant DDIs with anticancer drugs. Integration of DDI guidelines into the national electronic prescribing system is essential to achieve optimal efficacy and minimal toxicity in patients receiving anticancer therapy. A clear overview of clin-ically relevant DDIs with anticancer therapy provides clinicians with a structured, evidence-based and consensus-built tool for anticancer therapy surveillance. (c) 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)Personalised Therapeutic

Clinically relevant drug interactions with multikinase inhibitors: a review

Multikinase inhibitors (MKIs), including the tyrosine kinase inhibitors (TKIs), have rapidly become an established factor in daily (hemato)-oncology practice. Although the oral route of administration offers improved flexibility and convenience for the patient, challenges arise in the use of MKIs. As MKIs are prescribed extensively, patients are at increased risk for (severe) drug–drug interactions (DDIs). As a result of these DDIs, plasma pharmacokinetics of MKIs may vary significantly, thereby leading to high interpatient variability and subsequent risk for increased toxicity or a diminished therapeutic outcome. Most clinically relevant DDIs with MKIs concern altered absorption and metabolism. The absorption of MKIs may be decreased by concomitant use of gastric acid-suppressive agents (e.g. proton pump inhibitors) as many kinase inhibitors show pH-dependent solubility. In addition, DDIs concerning drug (uptake and efflux) transporters may be of significant clinical relevance during MKI therapy. Furthermore, since many MKIs are substrates for cytochrome P450 isoenzymes (CYPs), induction or inhibition with strong CYP inhibitors or inducers may lead to significant alterations in MKI exposure. In conclusion, DDIs are of major concern during MKI therapy and need to be monitored closely in clinical practice. Based on the current knowledge and available literature, practical recommendations for management of these DDIs in clinical practice are presented in this review

The Impact of Tobacco Control Policies on Smoking Among Socioeconomic Groups in Nine European Countries, 1990-2007

Background: It is uncertain whether tobacco control policies have contributed to a narrowing or widening of socioeconomic inequalities in smoking in European countries during the past two decades. This paper aims to investigate the impact of price and non-price related population-wide tobacco control policies on smoking by socioeconomic group in nine European countries between 1990 and 2007. Methods: Individual-level education, occupation and smoking status were obtained from nationally representative surveys. Country-level price-related tobacco control policies were measured by the relative price of cheapest cigarettes and of cigarettes in the most popular price category. Country-level non-price policies were measured by a summary score covering four policy domains: smoking bans or restrictions in public places and workplaces, bans on advertising and promotion, health warning labels, and cessation services. The associations between policies and smoking were explored using logistic regressions, stratified by education and occupation, and adjusted for age, Gross Domestic Product, period and country fixed effects. Results: The price of popular cigarettes and non-price policies were negatively associated with smoking among men. The price of the cheapest cigarettes was negatively associated with smoking among women. While these favorable effects were generally in the same direction for all socioeconomic groups, they were larger and statistically significant in lower socioeconomic groups only. Conclusions: Tobacco control policies as implemented in nine European countries, have probably helped to reduce the prevalence of smoking in the total population, particularly in lower socioeconomic groups. Widening inequalities in smoking may be explained by other factors. Policies with larger effects on lower socioeconomic groups are needed to reverse this trend. Implications: Socioeconomic inequalities in smoking widened between the 1990s and the 2000s in Europe. During the same period, there were intensified tobacco control policies in many European countries. It is uncertain whether tobacco control policies have contributed to a narrowing or widening of socioeconomic inequalities in smoking in European countries. This study shows that tobacco control policies as implemented in the available European countries have helped to reduce the prevalence of smoking in the total population, particularly in lower socioeconomic groups. Widening inequalities in smoking may be explained by other factors.Peer reviewe

Trends in educational inequalities in obesity in 15 European countries between 1990 and 2010

Background: The prevalence of obesity increased dramatically in many European countries in the past decades. Whether the increase occurred to the same extent in all socioeconomic groups is less known. We systematically assessed and compared the trends in educational inequalities in obesity in 15 different European countries between 1990 and 2010. Methods: Nationally representative survey data from 15 European countries were harmonized and used in a metaregression of trends in prevalence and educational inequalities in obesity between 1990 and 2010. Educational inequalities were estimated by means of absolute rate differences and relative rate ratios in men and women aged 30-64 years. Results: A statistically significant increase in the prevalence of obesity was found for all countries, except for Ireland (among men) and for France, Hungary, Italy and Poland (among women). Meta-regressions showed a statistically significant overall increase in absolute inequalities of 0.11% points [95% CI 0.03, 0.20] per year among men and 0.12% points [95% CI 0.04, 0.20] per year among women. Relative inequalities did not significantly change over time in most countries. A significant reduction of relative inequalities was found among Austrian and Italian women. Conclusion: The increase in the overall prevalence aligned with a widening of absolute but not of relative inequalities in obesity in many European countries over the past two decades. Our findings urge for a further understanding of the drivers of the increase in obesity in lower education groups particularly, and an equity perspective in population-based obesity prevention strategies.Peer reviewe

Rosuvastatin use increases plasma fibrinolytic potential: a randomised clinical trial

We conducted a study to assess the effect of rosuvastatin use on fibrinolysis in patients with previous venous thromboembolism (VTE). This was a post hoc analysis within the STAtins Reduce Thrombophilia (START) study (NCT01613794). Plasma fibrinolytic potential, fibrinogen, plasmin inhibitor, plasminogen activator inhibitor-1 (PAI-1) and thrombin-activatable fibrinolysis inhibitor (

Did the English strategy reduce inequalities in health? A difference-in-difference analysis comparing England with three other European countries

Background: Between 1997 and 2010, the English government pursued an ambitious programme to reduce health inequalities, the explicit and sustained commitment of which was historically and internationally unique. Previous evaluations have produced mixed results. None of these evaluations have, however, compared the trends in health inequalities within England with those in other European countries. We carried out an innovative analysis to assess whether changes in trends in health inequalities observed in England after the implementation of its programme, have been more favourable than those in other countries without such a programme. Methods: Data were obtained from nationally representative surveys carried out in England, Finland, the Netherlands and Italy for years around 1990, 2000 and 2010. A modified difference-in-difference approach was used to assess whether trends in health inequalities in 2000-2010 were more favourable as compared to the period 1990-2000 in England, and the changes in trends in inequalities after 2000 in England were then compared to those in the three comparison countries. Health outcomes were self-assessed health, long-standing health problems, smoking status and obesity. Education was used as indicator of socioeconomic position. Results: After the implementation of the English strategy, more favourable trends in some health indicators were observed among low-educated people, but trends in health inequalities in 2000-2010 in England were not more favourable than those observed in the period 1990-2000. For most health indicators, changes in trends of health inequalities after 2000 in England were also not significantly different from those seen in the other countries. Conclusions: In this rigorous analysis comparing trends in health inequalities in England both over time and between countries, we could not detect a favourable effect of the English strategy. Our analysis illustrates the usefulness of a modified difference-in-difference approach for assessing the impact of policies on population-level health inequalities.Peer reviewe