QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Résumé Extracto Full Text PDF Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Articles Ahead of Print [Order Reprint] Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Beltinger, J. Articles by Krähenbühl, S. Search for Related Content PubMed PubMed Citation Articles by Beltinger, J. Articles by Krähenbühl, S.

Hepatic Veno-Occlusive Disease Associated with Immunosuppressive Cyclophosphamide Dosing and Roxithromycin

Fellow in Gastroenterology, Division of Gastroenterology, University Hospital, Basel, Switzerland

Manuel Haschke, MD

Senior Fellow in Clinical Pharmacology & Toxicology, University Hospital

Priska Kaufmann, PhD

Fellow in Clinical Pharmacology, Department of Research, University Hospital

Marc Michot, MD

House Officer, Medical Intensive Care Unit, University Hospital

Luigi Terracciano, MD

Head, Molecular Pathology, Department of Pathology, University Hospital

Stephan Krähenbühl, MD PhD

Head, Division of Clinical Pharmacology & Toxicology, University Hospital

Reprints: Dr. Krähenbühl, Division of Clinical Pharmacology & Toxicology, University Hospital, CH-4031 Basel, Switzerland, fax 41 61 265 45 60, Kraehenbuehl{at}uhbs.ch

OBJECTIVE: To report on a patient developing hepatic veno-occlusive disease while being treated with immunosuppressive doses of cyclophosphamide (2 mg/kg).

CASE SUMMARY: A 66-year-old woman with autoimmune hemolytic anemia developed hepatic veno-occlusive disease while being treated with immunosuppressive cyclophosphamide 100 mg/day in combination with roxithromycin (total dose 600 mg/day). After all drugs were stopped, the patient recovered within 2 weeks. The Naranjo probability scale indicated a probable relationship between veno-occlusive disease and treatment with cyclophosphamide in this patient.

DISCUSSION: Since roxithromycin inhibits CYP3A4, which is involved with cyclophosphamide metabolism, a drug-drug interaction could have been responsible. In addition, roxithromycin is an inhibitor of the drug transporter P-glycoprotein, possibly leading to accumulation of cyclophosphamide in endothelial cells. Alternatively, since cyclophosphamide has been reported to induce apoptosis, roxithromycin could have rendered endothelial cells more vulnerable for apoptosis.

CONCLUSIONS: In specific patients, cyclophosphamide can be associated with hepatic veno-occlusive disease at immunosuppressive doses.

Key Words: apoptosis, cyclophosphamide, drug-drug interaction, roxithromycin

Published Online, March 7, 2006. www.theannals.com, DOI 10.1345/aph.1G441