e doses of 0.03% PROTOPIC Ointment, with 86% (12/14) of patients having peak blood concentrations below 2 ng/mL throughout the study.
The highest peak concentration was observed in one patient with 82% BSA involvement on day 1 following application of 0.03% PROTOPIC Ointment. The peak concentrations for this subject were 14.8 ng/mL on day 1 and 4.1 ng/mL on day 14. Mean peak tacrolimus blood concentrations following oral administration in pediatric liver transplant patients (n = 9) were 48.4± 27.9 ng/mL.
In a similar pharmacokinetic study with 61 enrolled pediatric patients (ages 6 -12 years) with atopic dermatitis, peak tacrolimus blood concentrations ranged from undetectable to 5.3 ng/mL after single or multiple doses of 0.1% PROTOPIC Ointment, with 91% (52/57) of eva luable patients having peak blood concentrations below 2 ng/mL throughout the study period. When detected, systemic exposure generally declined as treatment continued.
In clinical studies with periodic blood sampling, a similar distribution of tacrolimus blood levels was also observed, with 98% (509/522) of pediatric patients having a blood concentration below 2 ng/mL.
Renal Insufficiency
The effect of renal insufficiency on the pharmacokinetics of topically administered tacrolimus has not been eva luated. The mean clearance of IV administered tacrolimus in patients with renal dysfunction was similar to that of normal volunteers. On the basis of this information dose-adjustment is not expected to be needed.
Hepatic Insufficiency
The effect of hepatic insufficiency on the pharmacokinetics of topically administered tacrolimus has not been eva luated but dose-adjustment is not expected to be needed.
CLINICAL STUDIES
Three randomized, double-blind, vehicle-controlled, multi-center, phase 3 studies were conducted to eva luate PROTOPIC Ointment for the treatment of patients with moderate to severe atopic dermatitis. One (Pediatric) study included 351 patients 2-15 years of age, and the other two (Adult) studies included a total of 632 patients 15-79 years of age. Fifty-five percent (55%) of the patients were women and 27% were black. At baseline, 58% of the patients had severe disease and the mean body surface area (BSA) affected was 46%. Over 80% of patients had atopic dermatitis affecting the face and/or neck region. In these studies, patients applied either PROTOPIC Ointment 0.03%, PROTOPIC Ointment 0.1%, or vehicle ointment twice daily to 10% - 100% of their BSA for up to 12 weeks.
In the pediatric study, a significantly greater (p < 0.001) percentage of patients achieved at least 90% improvement based on the physician’s global eva luation of clinical response (the pre-defined primary efficacy endpoint) in the PROTOPIC Ointment 0.03% treatment group compared to the vehicle treatment group, but there was insufficient evidence that PROTOPIC Ointment 0.1% provided more efficacy than PROTOPIC Ointment 0.03%.
In both adult studies, a significantly greater (p < 0.001) percentage of patients achieved at least 90% improvement based on the physician’s global eva luation of clinical response in the PROTOPIC Ointment 0.03% and PROTOPIC Ointment 0.1% treatment groups compared to the vehicle treatment group. There was evidence that PROTOPIC Ointment 0.1% may provide more efficacy than PROTOPIC Ointment 0.03%. The difference in efficacy between PROTOPIC Ointment 0.1% and 0.03% was particularly evident in adult patients with severe disease at baseline |
