We are analyzing https://link.springer.com/article/10.1007/s40264-013-0047-5.

Title:
Cardiovascular Safety of Tyrosine Kinase Inhibitors: With a Special Focus on Cardiac Repolarisation (QT Interval) | Drug Safety
Description:
The development of tyrosine kinase inhibitors (TKI) represents a major milestone in oncology. However, their use has been found to be associated with serious toxicities that impinge on various vital organs including the heart. Sixteen TKIs have been approved for use in oncology as of 30 September 2012, and a large number of others are in development or under regulatory review. Cardiovascular safety of medicinal products is a major public health issue that has concerned all the stakeholders. This review focuses on three specific cardiovascular safety aspects of TKIs, namely their propensity to induce QT interval prolongation, left ventricular (LV) dysfunction and hypertension (both systemic and pulmonary). Analyses of information in drug labels, the data submitted to the regulatory authorities and the published literature show that a number of TKIs are associated with these undesirable effects. Whereas LV dysfunction and systemic hypertension are on-target effects related to the inhibition of ligand-related signalling pathways, QT interval prolongation appears to be an off-target class III electrophysiologic effect, possibly related to the presence of a fluorine-based pharmacophore. If not adequately managed, these cardiovascular effects significantly increase the morbidity and mortality in a population already at high risk. Hitherto, the QT effect of most QT-prolonging TKIs (except lapatinib, nilotinib, sunitinib and vandetanib) is relatively mild at clinical doses and has not led to appreciable morbidity clinically. In contrast, LV dysfunction and untreated hypertension have resulted in significant morbidity. Inevitably, dilemmas arise in determining the risk/benefit of a TKI therapy in an individual patient who develops any of these effects following the treatment of the TKI-sensitive cancer. QT interval prolongation, hypertension and LV dysfunction can be managed effectively by using reliable methods of measurement and careful monitoring of patients whose clinical management requires optimisation by a close collaboration between an oncologist and a cardiologist, an evolving subspecialty referred to as cardio-oncology. Despite their potential adverse clinical impact, the effects of TKIs on hypertension and LV function are generally inadequately characterised during their development. As has been the case with QT liability of drugs, there is now a persuasive case for a regulatory requirement to study TKIs systematically for these effects. Furthermore, since most of these novel drugs are studied in trials with relatively small sample sizes and approved on an expedited basis, there is also a compelling case for their effective pharmacovigilance and on-going reassessment of their risk/benefit after approval.
Website Age:
28 years and 1 months (reg. 1997-05-29).

Matching Content Categories {📚}

Education
Health & Fitness
Insurance

Content Management System {📝}

What CMS is link.springer.com built with?

Custom-built

No common CMS systems were detected on Link.springer.com, and no known web development framework was identified.

Traffic Estimate {📈}

What is the average monthly size of link.springer.com audience?

🌠 Phenomenal Traffic: 5M - 10M visitors per month

Based on our best estimate, this website will receive around 5,000,019 visitors per month in the current month.
However, some sources were not loaded, we suggest to reload the page to get complete results.

check SE Ranking
check Ahrefs
check Similarweb
check Ubersuggest
check Semrush

How Does Link.springer.com Make Money? {💸}

We can't figure out the monetization strategy.

Earning money isn't the goal of every website; some are designed to offer support or promote social causes. People have different reasons for creating websites. This might be one such reason. Link.springer.com has a revenue plan, but it's either invisible or we haven't found it.

Keywords {🔍}

article, google, scholar, pubmed, cas, kinase, cancer, inhibitors, hypertension, clin, tyrosine, drug, clinical, shah, cardiac, patients, cardiotoxicity, oncol, cardiovascular, pulmonary, safety, interval, drugs, imatinib, review, prolongation, pharmacol, arterial, effects, med, heart, treatment, accessed, protein, evaluation, res, herg, channel, development, tkis, ventricular, signalling, risk, sunitinib, therapy, potential, trials, toxicity, human, force,

Topics {✒️}

protocolid=115227&studyid=7fe7fadd-d3fa-4bd6-9bf5-0845ff2a2c90&compound=pazopanib&type=compound&letterrange=l ca/dhp-mps/prodpharma/sbd-smd/drug-med/index-eng eu/docs/en_gb/document_library/scientific_guideline/2009/09/wc500002841 eu/docs/en_gb/document_library/scientific_guideline/2009/09/wc500002879 gov/advisorycommittees/committeesmeetingmaterials/drugs/oncologicdrugsadvisorycommittee/default gov/scripts/cder/drugsatfda/index curl=pages/medicines/landing/epar_search platelet-derived growth factor month download article/chapter ligand-related signalling pathways kcnq1-kcne1 potassium channel amp-activated protein kinase tyrosine-kinase-targeting drugs src tyrosine kinases concentration-qt relationships play human ether-à tyrosine kinase inhibitors pressure overload-induced pulmonary vascular bed tyrosine kinase inhibitor protein-kinase mediated regulation vascular-disrupting agents european economic area qt/qtc interval prolongation phosphoinositide 3-kinase signalling eu/ema/index privacy choices/manage cookies human ether-a protein-coupled receptor full article pdf targeting kinase pathways krause ds pulmonary arterial hypertension related gene channel multikinase inhibitor sorafenib renal cancer patients review article published delayed ventricular repolarization ikr potassium channel ghofrani ha noncardiac vascular toxicities vegf/vegfr pathway macromolecular signalling complex related gene product small sample sizes targeting pdgf pathway anticancer-targeted therapies drug discov today t-cell lymphoma related subjects

Questions {❓}

Drug-induced QT interval prolongation: does ethnicity of the thorough QT study population matter?
Why do kinase inhibitors cause cardiotoxicity and what can be done about it?

Schema {🗺️}

WebPage:
      mainEntity:
         headline:Cardiovascular Safety of Tyrosine Kinase Inhibitors: With a Special Focus on Cardiac Repolarisation (QT Interval)
         description:The development of tyrosine kinase inhibitors (TKI) represents a major milestone in oncology. However, their use has been found to be associated with serious toxicities that impinge on various vital organs including the heart. Sixteen TKIs have been approved for use in oncology as of 30 September 2012, and a large number of others are in development or under regulatory review. Cardiovascular safety of medicinal products is a major public health issue that has concerned all the stakeholders. This review focuses on three specific cardiovascular safety aspects of TKIs, namely their propensity to induce QT interval prolongation, left ventricular (LV) dysfunction and hypertension (both systemic and pulmonary). Analyses of information in drug labels, the data submitted to the regulatory authorities and the published literature show that a number of TKIs are associated with these undesirable effects. Whereas LV dysfunction and systemic hypertension are on-target effects related to the inhibition of ligand-related signalling pathways, QT interval prolongation appears to be an off-target class III electrophysiologic effect, possibly related to the presence of a fluorine-based pharmacophore. If not adequately managed, these cardiovascular effects significantly increase the morbidity and mortality in a population already at high risk. Hitherto, the QT effect of most QT-prolonging TKIs (except lapatinib, nilotinib, sunitinib and vandetanib) is relatively mild at clinical doses and has not led to appreciable morbidity clinically. In contrast, LV dysfunction and untreated hypertension have resulted in significant morbidity. Inevitably, dilemmas arise in determining the risk/benefit of a TKI therapy in an individual patient who develops any of these effects following the treatment of the TKI-sensitive cancer. QT interval prolongation, hypertension and LV dysfunction can be managed effectively by using reliable methods of measurement and careful monitoring of patients whose clinical management requires optimisation by a close collaboration between an oncologist and a cardiologist, an evolving subspecialty referred to as cardio-oncology. Despite their potential adverse clinical impact, the effects of TKIs on hypertension and LV function are generally inadequately characterised during their development. As has been the case with QT liability of drugs, there is now a persuasive case for a regulatory requirement to study TKIs systematically for these effects. Furthermore, since most of these novel drugs are studied in trials with relatively small sample sizes and approved on an expedited basis, there is also a compelling case for their effective pharmacovigilance and on-going reassessment of their risk/benefit after approval.
         datePublished:2013-04-26T00:00:00Z
         dateModified:2013-04-26T00:00:00Z
         pageStart:295
         pageEnd:316
         sameAs:https://doi.org/10.1007/s40264-013-0047-5
         keywords:
            Imatinib
            Sorafenib
            Sunitinib
            Pulmonary Arterial Hypertension
            Gefitinib
            Drug Safety and Pharmacovigilance
            Pharmacology/Toxicology
         image:
         isPartOf:
            name:Drug Safety
            issn:
               1179-1942
               0114-5916
            volumeNumber:36
            type:
               Periodical
               PublicationVolume
         publisher:
            name:Springer International Publishing AG
            logo:
               url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
               type:ImageObject
            type:Organization
         author:
               name:Rashmi R. Shah
               affiliation:
                     name:Rashmi Shah Consultancy Ltd.
                     address:
                        name:Rashmi Shah Consultancy Ltd., Buckinghamshire, UK
                        type:PostalAddress
                     type:Organization
               email:[email protected]
               type:Person
               name:Joel Morganroth
               affiliation:
                     name:eResearch Technology
                     address:
                        name:eResearch Technology, Philadelphia, USA
                        type:PostalAddress
                     type:Organization
               type:Person
               name:Devron R. Shah
               affiliation:
                     name:Rashmi Shah Consultancy Ltd.
                     address:
                        name:Rashmi Shah Consultancy Ltd., Buckinghamshire, UK
                        type:PostalAddress
                     type:Organization
               type:Person
         isAccessibleForFree:
         hasPart:
            isAccessibleForFree:
            cssSelector:.main-content
            type:WebPageElement
         type:ScholarlyArticle
      context:https://schema.org
ScholarlyArticle:
      headline:Cardiovascular Safety of Tyrosine Kinase Inhibitors: With a Special Focus on Cardiac Repolarisation (QT Interval)
      description:The development of tyrosine kinase inhibitors (TKI) represents a major milestone in oncology. However, their use has been found to be associated with serious toxicities that impinge on various vital organs including the heart. Sixteen TKIs have been approved for use in oncology as of 30 September 2012, and a large number of others are in development or under regulatory review. Cardiovascular safety of medicinal products is a major public health issue that has concerned all the stakeholders. This review focuses on three specific cardiovascular safety aspects of TKIs, namely their propensity to induce QT interval prolongation, left ventricular (LV) dysfunction and hypertension (both systemic and pulmonary). Analyses of information in drug labels, the data submitted to the regulatory authorities and the published literature show that a number of TKIs are associated with these undesirable effects. Whereas LV dysfunction and systemic hypertension are on-target effects related to the inhibition of ligand-related signalling pathways, QT interval prolongation appears to be an off-target class III electrophysiologic effect, possibly related to the presence of a fluorine-based pharmacophore. If not adequately managed, these cardiovascular effects significantly increase the morbidity and mortality in a population already at high risk. Hitherto, the QT effect of most QT-prolonging TKIs (except lapatinib, nilotinib, sunitinib and vandetanib) is relatively mild at clinical doses and has not led to appreciable morbidity clinically. In contrast, LV dysfunction and untreated hypertension have resulted in significant morbidity. Inevitably, dilemmas arise in determining the risk/benefit of a TKI therapy in an individual patient who develops any of these effects following the treatment of the TKI-sensitive cancer. QT interval prolongation, hypertension and LV dysfunction can be managed effectively by using reliable methods of measurement and careful monitoring of patients whose clinical management requires optimisation by a close collaboration between an oncologist and a cardiologist, an evolving subspecialty referred to as cardio-oncology. Despite their potential adverse clinical impact, the effects of TKIs on hypertension and LV function are generally inadequately characterised during their development. As has been the case with QT liability of drugs, there is now a persuasive case for a regulatory requirement to study TKIs systematically for these effects. Furthermore, since most of these novel drugs are studied in trials with relatively small sample sizes and approved on an expedited basis, there is also a compelling case for their effective pharmacovigilance and on-going reassessment of their risk/benefit after approval.
      datePublished:2013-04-26T00:00:00Z
      dateModified:2013-04-26T00:00:00Z
      pageStart:295
      pageEnd:316
      sameAs:https://doi.org/10.1007/s40264-013-0047-5
      keywords:
         Imatinib
         Sorafenib
         Sunitinib
         Pulmonary Arterial Hypertension
         Gefitinib
         Drug Safety and Pharmacovigilance
         Pharmacology/Toxicology
      image:
      isPartOf:
         name:Drug Safety
         issn:
            1179-1942
            0114-5916
         volumeNumber:36
         type:
            Periodical
            PublicationVolume
      publisher:
         name:Springer International Publishing AG
         logo:
            url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
            type:ImageObject
         type:Organization
      author:
            name:Rashmi R. Shah
            affiliation:
                  name:Rashmi Shah Consultancy Ltd.
                  address:
                     name:Rashmi Shah Consultancy Ltd., Buckinghamshire, UK
                     type:PostalAddress
                  type:Organization
            email:[email protected]
            type:Person
            name:Joel Morganroth
            affiliation:
                  name:eResearch Technology
                  address:
                     name:eResearch Technology, Philadelphia, USA
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Devron R. Shah
            affiliation:
                  name:Rashmi Shah Consultancy Ltd.
                  address:
                     name:Rashmi Shah Consultancy Ltd., Buckinghamshire, UK
                     type:PostalAddress
                  type:Organization
            type:Person
      isAccessibleForFree:
      hasPart:
         isAccessibleForFree:
         cssSelector:.main-content
         type:WebPageElement
["Periodical","PublicationVolume"]:
      name:Drug Safety
      issn:
         1179-1942
         0114-5916
      volumeNumber:36
Organization:
      name:Springer International Publishing AG
      logo:
         url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
         type:ImageObject
      name:Rashmi Shah Consultancy Ltd.
      address:
         name:Rashmi Shah Consultancy Ltd., Buckinghamshire, UK
         type:PostalAddress
      name:eResearch Technology
      address:
         name:eResearch Technology, Philadelphia, USA
         type:PostalAddress
      name:Rashmi Shah Consultancy Ltd.
      address:
         name:Rashmi Shah Consultancy Ltd., Buckinghamshire, UK
         type:PostalAddress
ImageObject:
      url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
Person:
      name:Rashmi R. Shah
      affiliation:
            name:Rashmi Shah Consultancy Ltd.
            address:
               name:Rashmi Shah Consultancy Ltd., Buckinghamshire, UK
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Joel Morganroth
      affiliation:
            name:eResearch Technology
            address:
               name:eResearch Technology, Philadelphia, USA
               type:PostalAddress
            type:Organization
      name:Devron R. Shah
      affiliation:
            name:Rashmi Shah Consultancy Ltd.
            address:
               name:Rashmi Shah Consultancy Ltd., Buckinghamshire, UK
               type:PostalAddress
            type:Organization
PostalAddress:
      name:Rashmi Shah Consultancy Ltd., Buckinghamshire, UK
      name:eResearch Technology, Philadelphia, USA
      name:Rashmi Shah Consultancy Ltd., Buckinghamshire, UK
WebPageElement:
      isAccessibleForFree:
      cssSelector:.main-content

External Links {🔗}(322)

Analytics and Tracking {📊}

Google Tag Manager

Libraries {📚}

Clipboard.js
Prism.js

CDN Services {📦}

Crossref

4.96s.

LINK . SPRINGER . COM {}