Abstract
There is increasing evidence that tyrosine kinase inhibitors (TKIs) have significant blood glucose lowering effects. A 70-year old Caucasian male with liver cirrhosis Child-Pugh A, advanced hepatocellular carcinoma and diabetes had a stable glycemic control being treated with glibenclamide (3.5 mg twice daily). After the first daily dose of the TKI sorafenib (800 mg) the patient experienced acute nocturnal disorientation and somnolence with a corresponding blood glucose of 37 mg/dl. After administration of glucose intravenously the neurological disturbances were completely reversible.
As there was no intercurrent deterioration neither of hepatic nor of renal function, the severe hypoglycemia can likely be attributed to a drug-drug interaction of sorafenib with the sulfonylurea. The complete inhibition of the CYP2C9 and CYP3A4 mediated metabolic pathway of glibenclamide through sorafenib might have resulted in a rapid accumulation of glibenclamide. Profound blood glucose lowering effects of sorafenib might have additionally contributed to the hypoglycemic episode.
Keywords: Drug interaction, hypoglycemia, sorafenib, sulfonylureas.
Current Drug Safety
Title:Severe Hypoglycemia Due to Possible Interaction Between Glibenclamide and Sorafenib in a Patient with Hepatocellular Carcinoma
Volume: 8 Issue: 2
Author(s): Andreas Holstein, Peter Kovacs and Winfried Beil
Affiliation:
Keywords: Drug interaction, hypoglycemia, sorafenib, sulfonylureas.
Abstract: There is increasing evidence that tyrosine kinase inhibitors (TKIs) have significant blood glucose lowering effects. A 70-year old Caucasian male with liver cirrhosis Child-Pugh A, advanced hepatocellular carcinoma and diabetes had a stable glycemic control being treated with glibenclamide (3.5 mg twice daily). After the first daily dose of the TKI sorafenib (800 mg) the patient experienced acute nocturnal disorientation and somnolence with a corresponding blood glucose of 37 mg/dl. After administration of glucose intravenously the neurological disturbances were completely reversible.
As there was no intercurrent deterioration neither of hepatic nor of renal function, the severe hypoglycemia can likely be attributed to a drug-drug interaction of sorafenib with the sulfonylurea. The complete inhibition of the CYP2C9 and CYP3A4 mediated metabolic pathway of glibenclamide through sorafenib might have resulted in a rapid accumulation of glibenclamide. Profound blood glucose lowering effects of sorafenib might have additionally contributed to the hypoglycemic episode.
Export Options
About this article
Cite this article as:
Holstein Andreas, Kovacs Peter and Beil Winfried, Severe Hypoglycemia Due to Possible Interaction Between Glibenclamide and Sorafenib in a Patient with Hepatocellular Carcinoma, Current Drug Safety 2013; 8 (2) . https://dx.doi.org/10.2174/15748863113089990027
DOI https://dx.doi.org/10.2174/15748863113089990027 |
Print ISSN 1574-8863 |
Publisher Name Bentham Science Publisher |
Online ISSN 2212-3911 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Pharmacology and Therapeutic Applications of Enediyne Antitumor Antibiotics
Current Molecular Pharmacology The Circulating Endothelial Cell in Cancer: Towards Marker and Target Identification
Current Pharmaceutical Design Stem Cell Guardians – Old and New Perspectives in LSC Biology
Current Drug Targets Exposure and Genotoxicity Assessment Methodologies - The Case of Formaldehyde Occupational Exposure
Current Analytical Chemistry Brain Tumor Causes, Symptoms, Diagnosis and Radiotherapy Treatment
Current Medical Imaging Histone Deacetylase Inhibitors: A Review on Class-I Specific Inhibition
Mini-Reviews in Medicinal Chemistry Advancement and Strategies for the Development of Peptide-drug Conjugates: Pharmacokinetic Modulation, Role and Clinical Evidence against Cancer Management
Current Cancer Drug Targets Is Going for Cure in CML Targeting Aberrant Glycogen Synthase Kinase 3β?
Current Drug Targets Multidrug Resistance Through the Spectacle of P-Glycoprotein
Current Cancer Drug Targets Heat Shock Proteins: Therapeutic Perspectives in Inflammatory Disorders
Recent Patents on Inflammation & Allergy Drug Discovery Chemistry and Health Effects of Bioactive Compounds in Selected Culinary Aromatic Herbs
Current Nutrition & Food Science Anticancer Drugs in Liposomal Nanodevices: A Target Delivery for a Targeted Therapy
Current Topics in Medicinal Chemistry Characterizing the Relationship Between the Chemical Structures of Drugs and their Activities on Primary Cultures of Pediatric Solid Tumors
Current Medicinal Chemistry γ δ T Cell Modulation in Anticancer Treatment
Current Cancer Drug Targets Paving Roads for New Drugs in Oncology
Recent Patents on Anti-Cancer Drug Discovery The Dual Role of Tumor Necrosis Factor (TNF) in Cancer Biology
Current Medicinal Chemistry Novel Approaches for RNA Interference and their Application in Cancer Therapy
Current Pharmacogenomics Relevance of the Deletion Polymorphisms of the Glutathione S-Transferases GSTT1 and GSTM1 in Pharmacology and Toxicology
Current Drug Metabolism Tyrosine Kinases as Therapeutic Targets in BCR-ABL Negative Chronic Myeloproliferative Disorders
Current Drug Targets Targeting Signaling Pathways in Chronic Lymphocytic Leukemia
Current Cancer Drug Targets