A retrospective cohort study exploring diltiazem as a pharmaco‐enhancer for tacrolimus, in a post heart‐transplant setting

BACKGROUND A significant proportion of heart-transplant associated expenditure is attributable to immunosuppressants. Post-transplant hypertension adds to the pill-burden and subsequent costs. In this study, we describe the effect of diltiazem - the antihypertensive and pharmaco-enhancer - on reducing the required oral dose of tacrolimus. METHODS We included 17 recipients who had successfully undergone heart transplants but later developed post-transplant hypertension and were treated with diltiazem. Serum trough levels of the immunosuppressant tacrolimus were measured every two weeks. Required doses before and after the introduction of diltiazem were compared. Patients were assessed at each follow-up visit for any evidence of toxicity. Medication-related expenditure was estimated based on government-mandated standardized retail price. RESULTS The power of the study was 98.92% at α=0.05. The mean tacrolimus dose required prior to initiation of diltiazem was 5.85 ± 1.55 mg. After initiating diltiazem, the mean required doses reduced to 2.88 ± 1.24 mg(p<0.0001). Relatively, the required doses reduced by 52.4 ± 10.9 % - independently of age, sex, and dose of diltiazem. Medication-related monthly expenditure reduced by 50.3±10.4%. No patient demonstrated evidence of toxicity. CONCLUSIONS Concomitant use of diltiazem and tacrolimus can safely, effectively, and predictably reduce the required dose of tacrolimus and significantly reduce corresponding costs.