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 carried out in 1985, requiring a standard immunosuppressive regime of cyclosporine. Cyclosporine blood levels (trough levels) remained stable over the years. Drug Interaction: In 1995 the female patient started self-medication with St John's wort because of medium reactive depression. The standardized St John'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 and April 2000 showed decreased cyclosporine blood concentrations. The mean cyclosporine blood concentration before the comedication with St John's wort 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 was increased to a mean dosage of 8.2 mg/kg body weight daily (95% confidence 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 stopped. After stopping treatment with St John's wort, cyclosporine blood levels remained within the therapeutic range. Conclusion: Apart from an increased risk of graft rejection, the interaction 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 approximately 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 cyclosporine. It is of particular interest since this long-term observation uniquely reveals the raise of costs.