Diltiazem use in tacrolimus-treated renal transplant recipients J. Kothari MD, M. Nash BSc (Hons) , J. Zaltzman MSc MD FRCP(C) and G. V. Ramesh Prasad MBBS MSc FRCP(C) FACP St Michael’s Hospital, University of Toronto, Toronto, Canada SUMMARY Background: Calcium channel blockers are widely used in the treatment of post-transplant hyper- tension but have the potential for drug interaction with calcineurin inhibitors. Renal allograft out- comes when diltiazem is used with cyclosporine have been reported, but similar data with tacro- limus are not available. Methods: We performed a retrospective analysis of all our renal transplant recipients from March 1997 to March 2002 who were given tacrolimus, mycophenolate mofetil and prednisone. Patients were divided into two groups based on whether diltiazem was started in the first postoperative week. Outcome measures included renal function up to 2 years post-transplant, blood pressure (BP) control, tacrolimus exposure, and costs related to tacrolimus monitoring. Results: Sixty-four patients constituted the dil- tiazem group and 32 the control group. Their baseline characteristics were similar. The mean average daily dose of diltiazem used was 213Æ95 mg/day. There was no difference in renal function, graft survival, or patient survival over 2 years. BP control was similar although the dil- tiazem group required more medication. Diltiazem was discontinued in four patients due to side- effects. There was no difference in tacrolimus- related side-effects between the two groups. There was also no difference in tacrolimus exposure, cost related to tacrolimus monitoring, or combined costs when the expense of diltiazem was added. Conclusion: Diltiazem use is acceptably safe and efficacious in renal transplant recipients treated with tacrolimus-based immunosuppressive ther- apy. It can be considered as a first-line antihy- pertensive in these patients and is cost neutral for tacrolimus use. Keywords: antihypertensive therapy, calcium channel blockers, diltiazem, drug interaction, hypertension control, immunosuppressive drugs, safety INTRODUCTION Post-transplant hypertension, which is associated with diminished graft survival (1), is common and can be attributed in part to the widespread use of calcineurin-inhibitor agents (2). Calcium channel blockers (CCBs) are theoretically well suited for its treatment as they have a dominant dilatory effect on the afferent glomerular arteriole, where the vaso- constriction of calcineurin inhibitors is most prom- inent (3), and thus have the potential to reduce calcineurin inhibitor nephrotoxicity. Renal allograft and patient outcomes have been studied in cyclo- sporine-based immunosuppression when CCBs of the non-dihydropyridine classes, particularly dil- tiazem, have been used (4). However, there are no similar data on the use of diltiazem in tacrolimus- based immunosuppression. We therefore evaluated the safety and efficacy of diltiazem use as a first-line antihypertensive agent in renal transplant recipients who received tacrolimus-based immunosuppres- sion at our institution. As diltiazem also has an important pharmacokinetic interaction with tacro- limus (5), we analysed the financial implications associated with diltiazem use in these patients. METHODS Our institution is a tertiary care medical-surgical university-affiliated medical centre that currently provides post-transplant care to approximately Received 22 March 2004, Accepted 16 June 2004 Correspondence: G.V. Ramesh Prasad, Assistant Professor of Medicine, University of Toronto, Renal Transplant Program, St Michael’s Hospital, 61 Queen Street East, 9th Floor, Toronto, ON M5C 2T2, Canada. Tel.: (416) 867 3722; fax: (416) 867 3709; e-mail: prasadr@smh.toronto.on.ca Journal of Clinical Pharmacy and Therapeutics (2004) 29, 425–430 Ó 2004 Blackwell Publishing Ltd 425