Cyclosporine interaction with St John's wort (Hypericum perforatum) increases the risk of graft rejection and causes a raise of the daily medication costs

Anamnesis: A 55-year-old female kidney transplant patient has suffered from diabetes mellitus since being a child. A kidney transplantation was carrie d out in 1985, requiring a standard immunosuppressive regime of cyclosporin e. Cyclosporine blood levels (trough levels) remained stable over the years . Drug Interaction: In 1995 the female patient started self-medication with S t John's wort because of medium reactive depression. The standardized St Jo hn's, wort extract (sold under the brand name Neuroplant(R)) was taken at a dose of 300 mg three times daily. Laboratory investigations between 1995 a nd April 2000 showed decreased cyclosporine blood concentrations. The mean cyclosporine blood concentration before the comedication with St John's wor t was 210.0 ng/ml (95% confidence interval: 171.8-248.2 ng/ml), during the comedication 81.1 ng/ml (95% confidence interval: 60.8-101.4 ng/ml) and was without the herbal remedy 149.8 ngl/ml (95% confidence interval: 61.2-238. 5 ng/ml). Cyclosporine dosage during the comedication with St John's wort w as increased to a mean dosage of 8.2 mg/kg body weight daily (95% confidenc e interval: 7.0-9.4 mg/kg). In April 2000 the interaction of St John's wort with cyclosporine was suspected and the patient's self-medication was stop ped. After stopping treatment with St John's wort, cyclosporine blood level s remained within the therapeutic range. Conclusion: Apart from an increased risk of graft rejection, the interactio n also had cost implications because the dosage of this expensive drug had to be increased. In the period from 1995 to April 2000 an amount of approxi mately 15,300.- E (30,000.- DM) of cyclosporine medication was necessary to avoid transplant rejection. The trend of the graphs strongly suggests that the treatment with St John's wort was the cause of the drop in plasma cycl osporine. It is of particular interest since this long-term observation uni quely reveals the raise of costs.