Clinical evidence,mechanism, importance and management
2.7 nanograms/mL in a kidney transplant patient within 4 days of danazol 400mg to 1.2 g daily being started. Despite a reduction in danazol dosage to 600mg and then 400mg daily, her tacrolimus and creatinine serum levels remained high for one month until danazol was withdrawn. The reason is not known, but authors suggest that danazol possibly inhibits metabolism (demethylation and hydroxylation) of tacrolimus by liver so that it is cleared from body more slowly (See reference number 1). Tacrolimus is metabolised by cytochrome P450 isoenzyme CYP3A4, and danazol has been shown to inhibit this pathway (consider Statins + Danazol interaction). Therefore although this is an isolated case it seems possible that it will be of general significance. Monitor effects of concurrent use in any patient, reducing tacrolimus dosage as necessary.
1. Shapiro R,Venkataramanan R, Warty VS, Scantlebury VP, Rybka W, McCauley J, Fung JJ,Starzl TE. FK 506 interaction with danazol. Lancet (1993) 341, 1344–5.