Hepatic veno-occlusive disease associated with immunosuppressive cyclophosphamide dosing and roxithromycin.

Abstract

OBJECTIVE:

To report on a patient developing hepatic veno-occlusive disease while being treated with immunosuppressive doses of cyclophosphamide (< or =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.

• Authors: Johannes Beltinger, Manuel Haschke, Priska Kaufmann, Marc Michot, Luigi Terracciano, Stephan Krähenbühl
• Journal: The Annals of pharmacotherapy (Ann Pharmacother) Vol. 40 Issue 4 Pg. 767-70 (Apr 2006) ISSN: 1060-0280 [Print] United States
• PMID: 16595573 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Immunosuppressive Agents
• Roxithromycin
• Cyclophosphamide

Topics

• Aged
• Anemia, Hemolytic, Autoimmune (drug therapy)
• Cyclophosphamide (administration & dosage, adverse effects, therapeutic use)
• Female
• Hepatic Veno-Occlusive Disease (chemically induced)
• Humans
• Immunosuppressive Agents (administration & dosage, adverse effects, therapeutic use)
• Roxithromycin (administration & dosage, adverse effects, therapeutic use)