The use of other drugs to allow a lower dosage of cyclosporin to be used. Therapeutic and pharmacoeconomic considerations.
Since its discovery in 1970, and introduction into clinical practice in 1978, cyclosporin has become the most important immunosuppressive drug used to prevent organ transplant rejection. This has been achieved by virtue of the improved graft survival rates and adverse effect profiles in patients when compared with that of the older agents. Cyclosporin is substantially more expensive (both to provide and to monitor) however, and the magnitude of these costs may preclude its use, particularly where the transplant recipient is required to pay. Cyclosporin has a complex pharmacokinetic profile with poor absorption, extensive metabolism to more than 30 metabolites and considerable inter- and intrapatient variability. Many transplant centres routinely use drugs ("cyclosporin-sparing agents') to allow a reduction in the dosage of cyclosporin while maintaining therapeutic blood cyclosporin concentrations. The use of a second drug to affect the pharmacokinetic profile of a primary drug is not new, but the use of cyclosporin-sparing agents is a departure from previous practices in that this coprescription is primarily for economic reasons. The decision to use these agents (and the choice of agent) is based upon economic and other factors including the extent of the cyclosporin-sparing effect, the potential for additional therapeutic benefit and/or adverse effects. The coprescription of cyclosporin-sparing agents is ethically more acceptable where the transplant recipient is the economic beneficiary but where the savings accrue to a third party it is more difficult. Benefits to the community at large must be balanced against the risk of adverse effects to the patient. The use of cyclosporin-sparing agents may reduce compliance and hence, jeopardise transplant and/or recipient outcomes. The transplant recipient must be informed about the reasons for their use and advised to consult an experienced physician or pharmacist before altering the established drug regimen.
Jones
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TE
Pharmacy Department, Queen Elizabeth Hospital, Woodville South, Australia.
D001189:Aryl Hydrocarbon Hydroxylases; D001315:Australia; D016572:Cyclosporine / Q000008:administration & dosage* / Q000191:economics / Q000493:pharmacokinetics; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D004110:Diltiazem / Q000191:economics / Q000627:therapeutic use*; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000191:economics / Q000627:therapeutic use*; D006084:Graft Rejection / Q000191:economics / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000191:economics / Q000493:pharmacokinetics; D007654:Ketoconazole / Q000191:economics / Q000627:therapeutic use*; D009520:New Zealand; D016377:Organ Transplantation / Q000191:economics; D010089:Oxidoreductases, N-Demethylating / Q000037:antagonists & inhibitors
D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating; D004110:Diltiazem; D007654:Ketoconazole