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 micromol/liter, p = 0.01) with allopurinol, whereas it tended to decrease with sulfinpyrazone (160+/-35 and 154+/-48 micromol/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. 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.
Caforio
A L
AL
Department of Cardiology, University of Padova, Padova, Italy. acaforio@ux1.unipd.it
Gambino
A
A
Tona
F
F
Feltrin
G
G
Marchini
F
F
Pompei
E
E
Testolin
L
L
Angelini
A
A
Dalla Volta
S
S
Casarotto
D
D
D000493:Allopurinol / Q000009:adverse effects / Q000627:therapeutic use; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000009:adverse effects / Q000037:antagonists & inhibitors* / Q000097:blood; D004347:Drug Interactions; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000628:therapy; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000037:antagonists & inhibitors* / Q000097:blood; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D013442:Sulfinpyrazone / Q000494:pharmacology*; D014508:Urea / Q000097:blood; D014527:Uric Acid / Q000097:blood; D014528:Uricosuric Agents / Q000494:pharmacology*
D007166:Immunosuppressive Agents; D014528:Uricosuric Agents; D014527:Uric Acid; D000493:Allopurinol; D016572:Cyclosporine; D014508:Urea; D003404:Creatinine; D013442:Sulfinpyrazone