Elevation of cyclosporin A blood levels during carvedilol treatment in renal transplant patients.

In a consecutive study of 21 renal transplant patients suffering from chronic vascular rejection (CVR) we added the beta-receptor-blocking drug carvedilol to their regular medication. The purpose was to investigate possible pharmacokinetic interactions between carvedilol and cyclosporine (CsA), since carvedilol will soon be used in clinical trials in renal transplant patients with CVR. On the first day of the study the patients received 6.25 mg of carvedilol added to their daily medication. The dose was increased stepwise to 50 mg while the doses of other beta-blocking drugs were decreased. The goal was to exchange atenolol with carvedilol at a ratio of 2:1 when substituting atenolol with carvedilol. The patients' blood pressure was the final determinant of the dose of carvedilol. The trough levels of CsA were measured on days 1, 14, 30, 90 and 180. It was found that the blood levels of CsA increased when carvedilol was introduced. Thus, the doses of CsA had to be reduced in order to keep the blood levels within the therapeutic range. At 90 d, the daily doses of CsA had been reduced from 3.7 +/- 0.3 to 3.0 +/- 0.2 mg/kg BW (p < 0.001). The present results suggest an interaction between carvedilol and CsA that demands a 20% average reduction of CsA doses to maintain the CsA blood levels within the therapeutic range. However, the interaction shows a great interindividual variation, calling for careful monitoring of the CsA blood levels.