a) use of insulin for 30 or more consecutive days, with < 5 day gap, without a prior history of insulin dependent diabetes mellitus or non insulin dependent diabetes mellitus.

Development of Post Transplant Diabetes Mellitus by Race and by Treatment Group during First Year Post Kidney Transplantation in the Phase III study

Patient Race  Tacrolimus  CBIR 
No. of Patients at Risk  Patients Who Developed PTDMa  No. of Patients At Risk  Patients Who Developed PTDMa 
Black  41 15 (37%) 36 3 (8%)
Hispanic  17 5 (29%) 18 1 (6%)
Caucasian  82 10 (12%) 87 1 (1%)
Other  11 0 (0%) 10 1 (10%)
Total  151 30 (20%) 151 6 (4%)

a   use of insulin for 30 or more consecutive days, with < 5 day gap, without a prior history of  insulin dependent diabetes mellitus or non insulin dependent diabetes mellitus.

Insulin-dependent post-transplant diabetes mellitus was reported in 18% and 11% of tacrolimus-treated liver transplant patients and was reversible in 45% and 31% of these patients at 1 year post transplant, in the U.S. and European randomized studies, respectively (See Table below). Hyperglycemia was associated with the use of tacrolimus in 47% and 33% of liver transplant recipients in the U.S. and European randomized studies, respectively, and may require treatment (see ADVERSE REACTIONS ).
Incidence of Post Transplant Diabetes Mellitus and Insulin Use at 1 Year in Liver Transplant Recipients

Status of PTDMa  US Study  European Study 
Tacrolimus  CBIR  Tacrolimus  CBIR 
Patients at riskb  239 236 239 249
New Onset PTDMa  42 (18%) 30 (13%) 26 (11%) 12 (5%)
Patients still on insulin at 1 year 23 (10%) 19 (8%) 18 (8%) 6 (2%)

a) use of insulin for 30 or more consecutive days, with < 5 day gap, without a prior history of insulin dependent diabetes mellitus or non insulin dependent diabetes mellitus.

b) Patients without pretransplant history of diabetes mellitus.

Nephrotoxicity
Tacrolimus can cause nephrotoxicity, particularly when used in high doses. Nephrotoxicity was reported in approximately 52% of kidney transplantation patients and in 40% and 36% of liver transplantation patients receiving tacrolimus in the U.S. and European randomized trials, respectively (see ADVERSE REACTIONS ). More overt nephrotoxicity is seen early after transplantation, characterized by increasing serum creatinine and a decrease in urine output. Patients with impaired renal function should be monitored closely as the dosage of tacrolimus may need to be reduced. In patients with persistent elevations of serum creatinine who are unresponsive to dosage adjustments, consideration should be given to changing to another immunosuppressive therapy. Care should be taken in using tacrolimus with other nephrotoxic drugs. In particular, to avoid excess nephrotoxicity, tacrolimus should not be used simultaneously with cyclosporine. Tacrolimus or cyclosporine should be discontinued at lea