Supratherapeutic response to ezetimibe administered with cyclosporine.
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.


METHODS
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 < or = 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.


CONCLUSIONS
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 Unpublished data suggest a pharmacokinetic interaction between ezetimibe and cyclosporine that results in a significant 2.3- to 12-fold increase in exposure to total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 (> or = 5 mg/day) and titrated upward. Careful and consistent monitoring of patients on this combination is also advised.
Koshman
Sheri L
SL
Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
Lalonde
Lucille D
LD
Burton
Ilene
I
Tymchak
Wayne J
WJ
Pearson
Glen J
GJ
D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000069059:Atorvastatin; D001384:Azetidines / Q000008:administration & dosage / Q000627:therapeutic use*; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D004347:Drug Interactions; D000069438:Ezetimibe; D016027:Heart Transplantation / Q000009:adverse effects / Q000276:immunology*; D006538:Heptanoic Acids / Q000627:therapeutic use; D006801:Humans; D006949:Hyperlipidemias / Q000188:drug therapy / Q000209:etiology; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000188:drug therapy; D011758:Pyrroles / Q000627:therapeutic use
D000924:Anticholesteremic Agents; D001384:Azetidines; D006538:Heptanoic Acids; D007166:Immunosuppressive Agents; D011758:Pyrroles; D016572:Cyclosporine; D000069059:Atorvastatin; D000069438:Ezetimibe