nintedanib and Hemorrhage

Nintedanib is a synthetic orally active tyrosine kinase inhibitor, whose main action is to inhibit the receptors of the platelet-derived growth factor, fibroblast growth factor and vascular endothelial growth factor families. The drug also affects other kinases, including Src, Flt-3, LCK, LYN. Nintedanib is used in the treatment of idiopathic pulmonary fibrosis, chronic fibrosing interstitial lung diseases and lung cancer. The mechanism of action suggests that nintedanib should be considered one of the potential agents for inhibiting and revising the fibrosis process related to COVID-19 infections. Due to the known induction of coagulation pathways during COVID-19 infections, possible interaction between nintedanib and anticoagulant seems to be an extremely important issue. In theory, nintedanib could increase the bleeding risk, thrombosis and lead to thrombocytopenia. The data from clinical trials on the concomitant use of nintedanib and antithrombotic agents is very limited as this patient group was within the standard exclusion criteria. Nintedanib is an important therapeutic option, despite its interaction with anticoagulants. If anticoagulant therapy is necessary, the more effective and safer option is the concomitant administration of DOACs and nintedanib, especially when drug-monitored therapy will be used in patients at high risk of bleeding complications.

Topics: Anticoagulants; Antidotes; Antineoplastic Agents; Blood Coagulation Disorders; COVID-19; COVID-19 Drug Treatment; Drug Interactions; Hemorrhage; Humans; Idiopathic Pulmonary Fibrosis; Indoles; Lung Neoplasms; Protein Kinase Inhibitors; Risk Factors

In October 2016, a group of German IPF experts were invited by Boehringer Ingelheim to meet in Frankfurt with the aim, (a) to discuss relevant aspects of the management and treatment of idiopathic pulmonary fibrosis (IPF) using nintedanib; and, (b) to provide supportive advice for daily clinical practice with nintedanib. The resulting information compiled in this document is confined to practical issues regarding the use of nintedanib in patients with IPF. Where different therapeutic options were available, the choice of IPF medication was not discussed and the experts alluded to current guidelines for the diagnosis and treatment of IPF.The participants discussed a comprehensive spectrum of clinical questions related to 10 different topics, including patient-related aspects at initiation of IPF therapy, the treatment of anticoagulated IPF patients, and the handling of nintedanib-related adverse events such as gastrointestinal side effects and elevated liver enzymes. In addition, the experts evaluated therapeutic options for IPF patients with continuous disease progression, clinical scenarios that justify discontinuation of nintedanib treatment, and therapeutic options for IPF patients with an acute exacerbation or severe infection. Finally, the participants discussed the handling of nintendanib before/after elective surgical intervention (e. g. lung transplantation) and the current evidence for antifibrotic combination therapy in patients with IPF.For each topic discussed, the resulting information incorporates published evidence from clinical trials. In case of insufficient or lacking evidence, the experts have formulated recommendations based on their personal clinical experience and evaluation.. Im Oktober 2016 fand in Frankfurt auf Einladung von Boehringer Ingelheim ein Treffen deutscher IPF-Experten mit der Zielsetzung statt, praxisrelevante Aspekte der Behandlung der idiopathischen Lungenfibrose (IPF) mit Nintedanib zu erörtern und unterstützende Hilfestellungen für den klinischen Behandlungsalltag zu formulieren. Die resultierenden Hinweise dieses Dokumentes beschränken sich auf praktische Fragen und Erfahrungen zur Anwendung von Nintedanib bei IPF. Die Wahl des Medikaments bei Vorliegen verschiedener Therapieoptionen wurde hier nicht diskutiert. Hierzu verweisen die teilnehmenden Experten auf die aktuellen Leitlinien zur Diagnose und Therapie der IPF.Die Teilnehmer diskutierten anhand von 10 Themenbereichen ein umfassendes Spektrum klinischer Fragestellungen einer IPF-Behandlung mit Nintedanib. Hierzu zählten u. a. patientenbezogene Aspekte bei Therapiebeginn, die Behandlung antikoagulierter IPF-Patienten und der Umgang mit unerwünschten Arzneimittelwirkungen unter Nintedanib (z. B. gastrointestinale Nebenwirkungen, Leberenzymerhöhungen). Weiterhin erörterten die Experten Therapiemaßnahmen unter fortschreitender Krankheitsprogression des IPF-Patienten, klinische Umstände, die einen Therapieabbruch mit Nintedanib rechtfertigen, sowie therapeutische Handlungsoptionen bei akuter Exazerbation oder schwerer Infektion. Abschließend diskutierten die Teilnehmer die Vorgehensweise vor/nach elektiven Eingriffen (z. B. Lungentransplantation) unter Therapie mit Nintedanib und die gegenwärtige Evidenz für den Einsatz einer antifibrotischen Kombinationstherapie bei IPF-Patienten.In die zu jedem Themenbereich formulierten Hinweise einer IPF-Therapie mit Nintedanib ist die publizierte Evidenz aus klinischen Studien eingeflossen. Bei unzureichender oder fehlender Datenlage haben die Experten auf Grundlage eigener klinischer Erfahrungen und Einschätzungen Empfehlungen formuliert.

Topics: Anticoagulants; Clinical Competence; Combined Modality Therapy; Comorbidity; Disease Progression; Drug Interactions; Hemorrhage; Humans; Idiopathic Pulmonary Fibrosis; Indoles; Lung Transplantation

Nintedanib, a tyrosine kinase receptor inhibitor, may be associated with increased bleeding risk. Thus, patients with an inherited predisposition to bleeding, or those receiving therapeutic doses of anticoagulants or high-dose antiplatelet therapy, have been excluded from clinical trials of nintedanib in idiopathic pulmonary fibrosis (IPF).. Our objective was to examine real-world bleeding events in patients with IPF treated with antifibrotics, including those receiving anticoagulants and/or antiplatelet therapy.. The European MultiPartner IPF Registry (EMPIRE) enrolled 2794 patients with IPF: group A (1828: no anticoagulant or antiplatelet treatment), group B (227: anticoagulant treatment), group C (659: antiplatelet treatment), and group D (80: anticoagulant and antiplatelet treatment). Overall, 673 (24.1%) received nintedanib and 933 (33.4%) received pirfenidone. Bleeding events and their relationship to antifibrotic and anticoagulation treatment were characterized.. Group A patients, versus those in groups B, C, and D, were typically younger and generally had the lowest comorbidity rates. A higher proportion of patients in groups A and C, versus group B, received nintedanib. Pirfenidone, most common in group D, was more evenly balanced across groups. In patients with reported bleeding events, seven of eight received nintedanib (groups A, C, and D). Bleeding incidence was 3.0, 0, 1.3, and 18.1 per 10,000 patient-years (groups A, B, C, and D, respectively).. Real-world data from EMPIRE showed that patients on anticoagulant medications received nintedanib less frequently, perhaps based on its mechanism of action. Overall, bleeding incidence was low (0.29%: nintedanib 0.25%; pirfenidone 0.04%) and irrespective of anticoagulant or antiplatelet therapy received (P = 0.072).

Topics: Aged; Aged, 80 and over; Anticoagulants; Europe; Female; Hemorrhage; Humans; Idiopathic Pulmonary Fibrosis; Incidence; Indoles; Male; Middle Aged; Protein Kinase Inhibitors; Registries; Risk Factors