Table 6: Tacrolimus Whole Blood Trough Concentrations (Study 2)

Time Median (P10-P90a) tacrolimus whole blood trough concentrations (ng/mL)
Day 30 (N=174)  10.5 (6.3 to 16.8)
Day 60 (N=179)  9.2 (5.9 to 15.3) 
Day 120 (N=176)  8.3 (4.6 to 13.3) 
Day 180 (N=171)  7.8 (5.5 to 13.2) 
Day 365 (N=178)  7.1 (4.2 to 12.4) 

a) Range of Ctrough,Tac that excludes lowest 10% and highest 10% of Ctrough, Tac
The protocol-specified target cyclosporine whole blood concentrations (Ctrough,CsA) were 125 to 400 ng/mL for the first three months, and 100 to 300 ng/mL thereafter. The observed median Ctroughs, CsA approximated 280 ng/mL during the first three months and 190 ng/mL from month 4 to month 12.

Patients in both groups started MMF at 1g BID. The MMF dose was reduced to <2 g/day by month 12 in 62% of patients in the tacrolimus/MMF group (Table 7) and in 47% of patients in the cyclosporine/MMF group. Approximately 63% and 55% of these MMF dose reductions were because of adverse events in the tacrolimus/MMF group and the cyclosporine/MMF group, respectively.

Table 7: MMF Dose Over Time in the Tacrolimus/MMF group (Study 2)

Time period (Days)  Time-averaged MMF dose (g/day) a 
<2.0 2.0  >2.0
 0-30 (N=212)  25%  69%  6% 
0-90 (N=212)  41%  53%  6% 
0-180 (N=212)  52%  41%  7% 
0-365 (N=212)  62%  34%  4% 

Time-averaged MMF dose=(total MMF dose)/(duration of treatment)

a)    Percentage of patients for each time-averaged MMF dose range during various treatment periods. Two g/day of time-averaged MMF dose means that MMF dose was not reduced in those patients during the treatment periods.

INDICATIONS AND USAGE
Tacrolimus Capsule is indicated for the prophylaxis of organ rejection in patients receiving allogeneic liver, or kidney transplants. It is recommended that tacrolimus be used concomitantly with adrenal corticosteroids. In kidney transplant recipients, it is recommended that tacrolimus capsules be used in conjunction with azathioprine or mycophenolate mofetil (MMF).

CONTRAINDICATIONS
Tacrolimus Capsule is contraindicated in patients with a hypersensitivity to tacrolimus. Tacrolimus injection is contraindicated in patients with a hypersensitivity to HCO-60 (polyoxyl 60 hydrogenated castor oil).

WARNINGS
(See boxed WARNING .)

Post-Transplant Diabetes Mellitus Insulin-dependent post-transplant diabetes mellitus (PTDM) was reported in 20% of tacrolimus-treated kidney transplant patients without pretransplant history of diabetes mellitus in the Phase III study (See Tables Below). The median time to onset of PTDM was 68 days. Insulin dependence was reversible in 15% of these PTDM patients at one year and in 50% at 2 years post transplant. Black and Hispanic kidney transplant patients were at an increased risk of development of PTDM.

Incidence of Post Transplant Diabetes Mellitus and Insulin Use at 2 Years in Kidney Transplant Recipients in the Phase III study

Status of PTDM