Background: Beta-blockers are frequently used after cardiac transplantation for blood pressure control. There is no well-known interaction between beta-blockers and cyclosporine A (CsA). However, recent reports have suggested that carvedilol, but not metoprolol, modulates P-glycoprotein (P-gp), a membrane protein that regulates CsA absorption. We evaluated the effects of carvedilol and metoprolol on CsA level when initiated in cardiac transplant recipients.
Methods: Using our cardiac transplant database, we identified patients who were started on either carvedilol or metoprolol for blood pressure control. We then compared their CsA doses and levels before and within 2 weeks after the initiation of beta-blocker therapy.
Results: We found 20 patients taking metoprolol and 12 patients taking carvedilol. With initiation of metoprolol, CsA level decreased in 12 patients and increased in 8 patients. The mean CsA level before and after metoprolol initiation was 236 ng/ml and 253 ng/ml, respectively (p = 0.50). In an attempt to maintain a therapeutic CsA level, the mean CsA dose was not significantly adjusted (from a mean of 293 mg/day to a mean of 294 mg/day; p = 0.92). In the Carvedilol Group, CsA level increased in 10 of 12 patients. The mean CsA level before the initiation of carvedilol was 257 ng/ml. The mean CsA level after carvedilol initiation was 380 ng/ml (p = 0.009). In an attempt to maintain a therapeutic CsA level, the mean CsA dose was reduced by 10%, from a mean of 319 mg/day to a mean of 288 mg/day (p = 0.004).
Conclusion: Carvedilol, but not metoprolol, was associated with a significant increase in CsA levels after initiation in cardiac transplant recipients. Although carvedilol and CsA do not interact at the level of cytochrome P450 system, it appears that carvedilol influences CsA levels through its effects on P-gp. An average reduction of 10% is necessary on the CsA dose upon initiation of carvedilol, and close follow-up of the level is essential.