Sulfinpyrazone reduces cyclosporine levels. A new drug interaction in heart transplant recipients

Background: Management of cyclosporine (CsA)-associated hyperuricemia in heart transplantation (HT) is difficult. Because of the myelotoxicity of combined allopurinol and azathioprine, we tested sulfinpyrazone. Methods: We studied 120 HT recipients (109 men; mean age at HT, 52 +/- 10 years). All had received allopurinol for at least 6 months, which was stopped for 1 month before initiation of sulfinpyrazone. Mean follow-up from HT to onset of sulfinpyrazone (200 mg/day) was 59 +/- 41 months. We stopped the drug after 6 +/- 2 months. We compared CsA level and daily dose, serum creatinine, blood urea, and uric acid at onset and before interruption of sulfinpyrazone and, as control, in the last 6 months of allopurinol. Results: Mean uricemia decreased with allopurinol (0.58 +/- 0.12 vs 0.41 +/- 0.07 mmol/liter, p = 0.0001) as well as with sulfinpyrazone (0.51 +/- 0.13 vs 0.40 +/- 0.12 mmol/liter, p 0.0001). Mean creatinine increased (171 +/- 42 and 164 +/- 35 mu mol/liter, p = 0.01) with allopurinol, whereas it tended to decrease with sulfinpyrazone (160 +/- 35 and 154 +/- 48 mu mol/liter, p = NS). Mean urea did not change with allopurinol (14 +/- 5 vs 15 +/- 7 mmol/liter, p = NS), but fell with sulfinpyrazone (14.01 +/- 5 vs 12.60 +/- 5 mmol/liter, p = 0.0004). Mean CsA levels were constant with allopurinol (193 +/- 73 vs 188 +/- 65 ng/ml, p = NS), although CsA dose was slightly reduced (2.7 +/- 0.8 vs 2.6 +/- 0.8 mg/kg/day, p = 0.007). Conversely, CsA levels dropped with sulfinpyrazone (183 +/- 89 vs 121 +/- 63 ng/ml, p = 0.0001) despite an increase in CsA daily dose (2.6 +/- 0.9 vs 2.8 +/- 0.9 mg/kg/day, p = 0.0001). Two subjects were treated for acute rejection. We observed no other side effects. Conclusions: In HT recipients sulfinpyrazone, as an alternative to allopurinol, is effective in achieving metabolic control of hyperuricemia. However, this drug reduced CsA levels, thus the risk of rejection is present.