OKT3 therapy increases cyclosporine blood levels

Numerous drugs have been reported to alter cyclosporine (CSA) blood levels, most notably, those drugs that interfere with cytochrome P450 metabolism. Our clinical experience suggested that OKT3 therapy may alter CSA blood levels as well. The purpose of this study was to assess the effect of OKT3 therapy on CSA trough blood levels. We reviewed medical records of all CSA-treated renal transplant recipients during a 3-yr period to identify patients who received antilymphocyte induction therapy. Patients receiving drugs known to interact with CSA were excluded from analysis. The study population (n=33) was divided into two groups: the OKT3 group consisting of 17 patients who received OKT3 therapy for 7 d post-transplant (OKT3 group) and the control group consisting of 16 patients who received ALG induction therapy for 7 d post-transplant (ALG group). Oral CSA (14 mg/kg) was administered preoperatively. Postoperatively, oral CSA (4 mg/kg) was administered twice daily, in addition to corticosteroids and azathioprine. We evaluated CSA through levels on days 1, 3, 5, and 7 of antilymphocyte therapy and 3 d following completion of antilymphocyte therapy. On days 1 and 3, CSA trough levels did not differ between the two groups. However, median CSA trough levels (HPLC) were significantly higher among OKT3-treated patients on day 5 of therapy (265 ng/ml), as compared to ALG-treated patients (136 ng/ml; p < 0.0001; Mann-Whitney U-test). On days 7 and 10, CSA trough levels did not differ between the two groups. CSA doses, however, had been adjusted based on levels obtained on day 5. We conclude that OKT3 therapy causes a significant rise in CSA trough levels. Recognition of this potential drug interaction is essential in titrating CSA doses in the early post-transplant period to minimize risks of CSA toxicity or early rejection following induction therapy.