Background: Elevation of the international normalized ratio and bleeding complications has been reported in patients taking warfarin concomitantly with tyrosine kinase inhibitors such as gefitinib and erlotinib.
Objective: To assess the frequency, degree, and onset of international normalized ratio elevation in patients receiving warfarin with gefitinib or erlotinib, and changes cytochrome P450 2C9 activity.
Methods: This retrospective, single-center, observational study compared international normalized ratio values during the treatment with warfarin in the absence and presence of the tyrosine kinase inhibitors, gefitinib, and erlotinib. In addition, the inhibitory effect of tyrosine kinase inhibitors on cytochrome P450 2C9 activity was screened in an study.
Results: Compared with international normalized ratio at the baseline significant ( < 0.05) international normalized ratio elevations were observed in the majority of the patients (5/6 patients with gefitinib, 83.3%; 6/7 patients with erlotinib, 85.7%) during concurrent therapy. The international normalized ratio was increased 1.8- and 1.6-fold relative to the baseline value, on median, in the presence of gefitinib and erlotinib, respectively, and the onset of international normalized ratio elevation was observed at a median of seven days and nine days, respectively. (S)-warfarin 7-hydroxylation activity was inhibited by 36% in the presence of 1 µM gefitinib and 27% by 10 µM erlotinib, which are comparable to the steady-state plasma levels of these tyrosine kinase inhibitors after standard dosing.
Conclusion: In most patients, international normalized ratio elevation was observed within two weeks of the start of concomitant therapy with warfarin and gefitinib or erlotinib. To avoid excessive anticoagulant response by warfarin, international normalized ratio should be carefully monitored weekly and dosage adjustment of warfarin might be recommended during the first month after the start of concurrent tyrosine kinase inhibitor therapy.
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http://dx.doi.org/10.1177/1078155218801061 | DOI Listing |
BMC Plant Biol
January 2025
College of Life Sciences, Nanjing Normal University, Nanjing, 210023, China.
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January 2025
Department of Child Life and Health, University of Edinburgh Institute for Regeneration and Repair, Edinburgh, UK.
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Endoscopy
January 2025
Gastroenterology and Hepatology, The University of Texas Health Science Center at San Antonio, San Antonio, United States.
Introduction EUS-guided gall bladder drainage (EUS-GBD) for management of symptomatic gallbladder disease has been shown to be safe and effective in high surgical risk patients with data lacking in patients with cirrhosis. We sought to study the safety and effectiveness of EUS-GBD in cirrhotic compared to non-cirrhotic patients. Methods Retrospective review of patients who underwent EUS-GBD at four (3 US and 1 Spain) international tertiary care centers.
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January 2025
CAS Key Laboratory of Mountain Ecological Restoration and Bio-resources Utilization, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, China. Electronic address:
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December 2024
Key Laboratory of Lake and Watershed Science for Water Security, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, Nanjing 211135, China; Sino-Danish Centre for Education and Research, University of Chinese Academy of Sciences, Beijing 100039, China; Poyang Lake Wetland Research Station, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, Jiujiang 332899, China. Electronic address:
Flash drought (FD) events induced by climate change may disrupt the normal hydrological regimes of floodplain lakes and affect the plant-microbe mediated dissimilatory nitrate reduction (DNR), i.e., denitrification, anammox and dissimilatory nitrate reduction to ammonium (DNRA), thus having important consequences for nitrous oxide (NO) emissions and nitrogen (N) retention.
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