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.

Over-the-counter medications in cardiac transplant recipients: guidelines for use.

OBJECTIVE: The purpose of this article is to review the pathophysiology of the denervated heart and the factors that need to be considered before recommending the use of over-the-counter (OTC) medications in the cardiac transplant recipient. DATA SOURCES: Pharmacology and therapeutic textbooks, English-language journal articles, and physiology textbooks published between 1969 and 1991. DATA EXTRACTION: Case reports, controlled case studies, and textbook chapters evaluating drug interactions with immunosuppressive agents were reviewed. The effects of various OTC medications on the denervated heart were examined and relevant material was extrapolated. DATA ANALYSIS: The number of cases or studies in which a particular effect or interaction occurred was reported. Those findings that were less well documented were either identified as such or were not included in the review. DATA SYNTHESIS: Common pharmacokinetic and pharmacodynamic interactions with the primary immunosuppressive agents (e.g., cyclosporine, azathioprine, prednisone) are reviewed. The physiology and altered responses of the denervated heart to various medications are also explained. Using this information recommendations are given for the use and monitoring of OTC analgesics, antacids, laxatives, sleep aids, stimulants, and other medications that may be used in the cardiac transplant recipient. CONCLUSIONS: Many OTC medications can be used safely in the cardiac transplant recipient. In each situation, risk/benefit assessments must always be made and therapy should be monitored closely. Most important, patients should always notify the transplant team before adding an OTC product to their immunosuppressive regimen.