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Supratherapeutic Response to Ezetimibe Administered with Cyclosporine

at time of writing, PharmD Student, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada; now, Clinical Postdoctoral Fellow in Ambulatory Cardiology, Division of Cardiology, University of Alberta, Edmonton, Alberta, Canada

Lucille D Lalonde, MD FRCPC

Associate Professor of Medicine, Faculty of Medicine and Dentistry; Staff Cardiologist, Medical Director, CardiacEASE Clinic, Division of Cardiology, University of Alberta

Ilene Burton, RN

Outpatient Nurse Coordinator, Cardiac Transplant Program, University of Alberta Hospital

Wayne J Tymchak, MD FRCPC

Professor of Medicine, Faculty of Medicine and Dentistry; Staff Cardiologist, Medical Director, Coronary Intensive Care Unit; Deputy Divisional Director, Division of Cardiology, University of Alberta

Glen J Pearson, PharmD FCSHP

Associate Professor of Medicine, Faculty of Medicine and Dentistry; Co-Director, Cardiac Transplant Clinic; Deputy Medical Director and Director of Research, Cardiovascular Risk Reduction Clinic, Division of Cardiology, University of Alberta

Reprints: Dr. Pearson, Division of Cardiology, University of Alberta, Ste. 2E1.24, Walter Mackenzie Health Sciences Centre, 8440-112th St., Edmonton, AB T6G 2B7, Canada, fax 780/407-1496, Glen.Pearson{at}ualberta.ca

OBJECTIVE: To report the case of a patient who underwent orthotopic heart transplant (OHT) and demonstrated a supratherapeutic response to ezetimibe when administered with cyclosporine.

CASE SUMMARY: Ezetimibe 10 mg/day was added to the lipid-lowering regimen (atorvastatin 40 mg/day) of a 64-year-old male patient after OHT to achieve a target low-density lipoprotein cholesterol (LDL-C) level 97 mg/dL, as recommended by national guidelines. After 2 months of ezetimibe, the patient's LDL-C level had decreased by 60% to 51 mg/dL. Subsequently, the dose of ezetimibe was reduced to 5 mg/day and, after another 2 months, a repeat lipid panel revealed LDL-C 57 mg/dL.

DISCUSSION: Hyperlipidemia is a common problem among heart transplant recipients. Combination therapy using a statin plus ezetimibe appears to be an attractive option to achieve target lipid levels in this population. However, the manufacturer warns that ezetimibe should be administered cautiously in patients concomitantly receiving cyclosporine. Unpublished data suggest a pharmacokinetic interaction between ezetimibe and cyclosporine that results in a significant 2.3- to 12-fold increase in exposure to total ezetimibe. An objective causality assessment in this case revealed that this supratherapeutic LDL-C reduction was probably related to coadministration of ezetimibe and cyclosporine. A potential mechanism to explain this interaction might be an alteration in glucuronidation induced by cyclosporine.

CONCLUSIONS: When ezetimibe is prescribed for patients concomitantly receiving cyclosporine, it should be initiated at a lower than recommended dose (5 mg/day) and titrated upward. Careful and consistent monitoring of patients on this combination is also advised.

Key Words: cyclosporine, ezetimibe, heart transplant

Published Online, July 19, 2005. www.theannals.com, DOI 10.1345/aph.1G015

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