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

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

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.

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.

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