Cotreatment with lenvatinib and warfarin potassium caused prothrombin time prolongation.
hepatocellular carcinoma
lenvatinib
prothrombin time
warfarin potassium
Journal
Hepatology research : the official journal of the Japan Society of Hepatology
ISSN: 1386-6346
Titre abrégé: Hepatol Res
Pays: Netherlands
ID NLM: 9711801
Informations de publication
Date de publication:
Nov 2019
Nov 2019
Historique:
received:
18
01
2019
revised:
30
04
2019
accepted:
13
05
2019
pubmed:
24
5
2019
medline:
24
5
2019
entrez:
24
5
2019
Statut:
ppublish
Résumé
Lenvatinib is approved as a standard systemic therapy for unresectable hepatocellular carcinoma (HCC) patients; however, experience with lenvatinib in clinical practice is insufficient. We present the case of a patient with advanced HCC whose prothrombin time - international normalized ratio (PT-INR) was elevated after cotreatment with lenvatinib and warfarin potassium. The patient was a 26-year-old man with congenital abnormalities who had to take warfarin potassium because he had a mechanical heart valve. He was diagnosed with unresectable HCC at 24 years old and was treated by transcatheter arterial chemoembolization and transcatheter arterial infusion. After some interventional radiology treatments, lenvatinib was started. After 4 days of treatment with lenvatinib and warfarin potassium, his PT-INR increased to 4.13, and the treatment had to be stopped. No changes were observed in other Child-Pugh score factors. The elevation in the PT-INR after cotreatment with lenvatinib and warfarin potassium was thought to be caused by pharmacological effects of concurrent use or pharmacological sensitivity to warfarin potassium in this patient with liver dysfunction. The PT-INR must be monitored when lenvatinib is given to advanced HCC patients taking warfarin potassium.
Types de publication
Journal Article
Langues
eng
Pagination
1357-1361Informations de copyright
© 2019 The Japan Society of Hepatology.
Références
Kudo M, Finn RS, Qin S et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet 2018; 391(10126): 1163-1173.
Eso Y, Marusawa H. Novel approaches for molecular targeted therapy against hepatocellular carcinoma. Hepatol Res 2018; 48: 597-607.
Takeda H, Nishijima N, Nasu A et al. Long-term antitumor effect of lenvatinib on unresectable hepatocellular carcinoma with portal vein invasion. Hepatol Res 2019; 49: 594-599.
Hill RB, Gaetani S, Paolucci AM et al. Vitamin K and biosynthesis of protein and prothrombin. J Biol Chem 1968; 243: 3930-3939.
Berkner KL. Vitamin K-dependent carboxylation. Vitam Horm 2008; 78: 131-156.
Blanchard RA, Furie BC, Jorgensen M, Kruger SF, Furie B. Acquired vitamin K-dependent carboxylation deficiency in liver disease. N Engl J Med 1981; 305: 242-248.
Yang LQ, Li SJ, Cao YF et al. Different alterations of cytochrome P450 3A4 isoform and its gene expression in livers of patients with chronic liver diseases. World J Gastroenterol 2003; 9: 359-363.
Chen H, Shen ZY, Xu W et al. Expression of P450 and nuclear receptors in normal and end-stage Chinese livers. World J Gastroenterol 2014; 20: 8681-8690.
Eble, West BD, Link KP. A comparison of the isomers of warfarin. Biochem Pharmacol 1966; 15: 1003-1006.
Kaminsky LS, Zhang ZY. Human P450 metabolism of warfarin. Pharmacol Ther 1997; 73: 67-74.
Flora DR, Rettie AE, Brundage RC, Tracy TS. CYP2C9 genotype-dependent warfarin pharmacokinetics: impact of CYP2C9 genotype on R- and S-warfarin and their oxidative metabolites. J Clin Pharmacol 2017; 57: 382-393.
Li X, Liu R, Yan H et al. Effect of CYP2C9-VKORC1 interaction on warfarin stable dosage and its predictive algorithm. J Clin Pharmacol 2015; 55: 251-257.
Food and Drug Administration (FDA), Prescribing information for lenvatinib. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206947s000lbl.pdf Accessed January 18, 2019.
Inoue K, Mizuo H, Kawaguchi S, Fukuda K, Kusano K, Yoshimura T. Oxidative metabolic pathway of lenvatinib mediated by aldehyde oxidase. Drug Metab Dispos 2014; 42: 1326-1333.
Food and Drug Administration (FDA), Prescribing information for sorafenib. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021923s008s009lbl.pdf Accessed January 18, 2019.
Food and Drug Administration (FDA), Prescribing information for regorafenib. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203085lbl.pdf Accessed January 18, 2019.
Kitade H, Hiromasa YA, Hokkoku K et al. Elevated prothrombin time/international normalized ratio associated with concurrent administration of regorafenib and warfarin in a patient with advanced colorectal cancer. J Pharm Health Care Sci 2016; 2: 15.
Eikelboom JW, Connolly SJ, Brueckmann M et al. Dabigatran versus warfarin in patients with mechanical heart valves. N Engl J Med 2013; 369: 1206-1214.
Matsuyama K, Matsumoto M, Sugita T et al. Anticoagulant therapy in Japanese patients with mechanical mitral valves. Circ J 2002; 66: 668-670.
Moretti LV, Montalvo RO. Elevated international normalized ratio associated with concurrent use of sorafenib and warfarin. Am J Health Syst Pharm 2009; 66: 2123-2125.
Laber DA, Mushtaq M. Compassionate use of sorafenib in patients with advanced renal cell cancer. Clin Genitourin Cancer 2009; 7: 34-38.
Ikeda M, Okusa T, Mitsunaga S et al. Safety and pharmacokinetics of lenvatinib in patients with advanced hepatocellular carcinoma. Clin Cancer Res 2016; 22: 1385-1394.
Boss DS, Glen H, Beijnen JH et al. A phase I study of E7080, a multitargeted tyrosine kinase inhibitor, in patients with advanced solid tumours. Br J Cancer 2012; 106: 1598-1604.