Considerations for using ketoconazole in solid organ transplant recipients receiving cyclosporine immunosuppression.
Drug interactions involving cyclosporine following transplantation are a challenging issue for the transplant clinician. This is especially true when ketoconazole is the second agent used in conjunction with cyclosporine. Because both agents are metabolized by the cytochrome P-450 IIIA4 enzyme system, cyclosporine levels rise dramatically in the presence of ketoconazole. Many other agents interact with ketoconazole, either by competitive enzyme inhibition in the liver and gastrointestinal tract, or by reducing the absorption of ketoconazole by agents that increase the pH of the gastrointestinal tract. Despite the potential cost savings when using ketoconazole to reduce cyclosporine doses, adverse effects associated with ketoconazole put patients at risk when using this combination. Close monitoring of cyclosporine levels is imperative when adding ketoconazole to cyclosporine, and once the dosage adjustments are complete, the addition of a third drug that interacts with either cyclosporine or ketoconazole could result in an unexpected rejection episode or toxic cyclosporine side effect.
Chapman
S A
SA
Minneapolis Heart Institute/Foundation, Minneapolis, MN, USA.
Lake
K D
KD
Solbrack
D F
DF
Milfred
S K
SK
Marshall
P S
PS
Kamps
M A
MA
D000935:Antifungal Agents / Q000627:therapeutic use*; D016572:Cyclosporine / Q000627:therapeutic use*; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects; D004347:Drug Interactions; D016903:Drug Monitoring; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007654:Ketoconazole / Q000627:therapeutic use*; D006899:Mixed Function Oxygenases / Q000187:drug effects; D016377:Organ Transplantation / Q000009:adverse effects*
D000935:Antifungal Agents; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; D007654:Ketoconazole