THE USE OF OTHER DRUGS TO ALLOW A LOWER DOSAGE OF CYCLOSPORINE TO BE USED - THERAPEUTIC AND PHARMACOECONOMIC CONSIDERATIONS

Since its discovery in 1970, and introduction into clinical practice i n 1978, cyclosporin has become the most important immunosuppressive dr ug used to prevent organ transplant rejection. This has been achieved by virtue of the improved graft survival rates and adverse effect prof iles in patients when compared with that of the older agents. Cyclospo rin is substantially more expensive (both to provide and to monitor) h owever, and the magnitude of these costs may preclude its use, particu larly where the transplant recipient is required to pay.Cyclosporin ha s a complex pharmacokinetic profile with poor absorption, extensive me tabolism to more than 30 metabolites and considerable inter- and intra patient variability. Many transplant centres routinely use drugs ('cyc losporin-sparing agents') to allow a reduction in the dosage of cyclos porin while maintaining therapeutic blood cyclosporin concentrations. The use of a second drug to affect the pharmacokinetic profile of a pr imary drug is not new, but the use of cyclosporin-sparing agents is a departure from previous practices in that this coprescription is prima rily for economic reasons. The decision to use these agents (and the c hoice of agent) is based upon economic and other factors including the extent of the cyclosporin-sparing effect, the potential for additiona l therapeutic benefit and/or adverse effects. The coprescription of cy closporin-sparing agents is ethically more acceptable where the transp lant recipient is the economic beneficiary but where the savings accru e 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 pati ent. The use of cyclosporin-sparing agents may reduce compliance and h ence, 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.