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
-
Structure, Substrate Complexation and Reaction Mechanism of Bacterial Asparaginases
Current Chemical Biology MicroRNAs and Cancer; an Overview
Current Pharmaceutical Biotechnology Immunotoxins Constructed with Ribosome-Inactivating Proteins and their Enhancers: A Lethal Cocktail with Tumor Specific Efficacy
Current Pharmaceutical Design A Virtual Screening Approach for the Identification of High Affinity Small Molecules Targeting BCR-ABL1 Inhibitors for the Treatment of Chronic Myeloid Leukemia
Current Topics in Medicinal Chemistry Restoring TRAIL Induced Apoptosis Using Naturopathy. Hercules Joins Hand with Nature to Triumph Over Lernaean Hydra
Current Genomics Antimicrobial Activity of New 2-Thioxo-benzo[g]quinazolin-4(3H)-one Derivatives
Medicinal Chemistry Histone Deacetylase Inhibitors In Inflammatory Disease
Current Topics in Medicinal Chemistry The Function and Regulation of BMP6 in Various Kinds of Stem Cells
Current Pharmaceutical Design Current Perspective of Natural Alkaloid Carbazole and its Derivatives as Antitumor Agents
Anti-Cancer Agents in Medicinal Chemistry Restoration of Chemoresistance Mechanism by Novel Drug Therapies in Breast Cancer Cell Lines
Current Drug Therapy Determination of 7,12-Dimethylbenz[a]Anthracene in Orally Treated Rats by High-Performance Liquid Chromatography and Transfer Stripping Voltammetry
Combinatorial Chemistry & High Throughput Screening Going 3D – Cell Culture Approaches for Stem Cell Research and Therapy
Current Tissue Engineering (Discontinued) MicroRNAs in Cancer: Small Molecules, Big Chances
Anti-Cancer Agents in Medicinal Chemistry Biology and Clinical Relevance of Mannose-Binding Lectin
Drug Design Reviews - Online (Discontinued) Pharmacological Aspects of the Enzastaurin-Pemetrexed Combination in Non-Small Cell Lung Cancer (NSCLC)
Current Drug Targets Ginkgo biloba Extract in Vascular Protection: Molecular Mechanisms and Clinical Applications
Current Vascular Pharmacology Novel Drug Therapies for Fertility Preservation in Men Undergoing Chemotherapy: Clinical Relevance of Protector Agents
Current Medicinal Chemistry Phosphatidylinositol 3-Kinase Isoforms as Novel Drug Targets
Current Drug Targets Cutoff Values of D-Dimer and FDP in Plasma for the Diagnosis of Thrombosis
Vascular Disease Prevention (Discontinued) Compendious Review on Bioactive Constituents and Pharmacotherapeutic Profile of Heliotropium indicum Linn
The Natural Products Journal