*hr and the increase in Cmax was from 4.4 ng/mL to 7.3 ng/mL.
Deferasirox:Co-administration of deferasirox (30 mg/kg/day for 4 days) and repaglinide (single dose of 0.5 mg) resulted in an increase in repaglinide systemic exposure (AUC) to 2.3-fold of control and an increase in Cmax of 62% (see PRECAUTIONS,Drug-Drug Interactions).
Renal Insufficiency:Single-dose and steady-state pharmacokinetics of repaglinide were compared between patients with type 2 diabetes and normal renal function (CrCl > 80 mL/min), mild to moderate renal function impairment (CrCl = 4080 mL/min), and severe renal function impairment (CrCl = 2040 mL/min). Both AUC and Cmax of repaglinide were similar in patients with normal and mild to moderately impaired renal function (mean values 56.7 ng/mL*hr vs 57.2 ng/mL*hr and 37.5 ng/mL vs 37.7 ng/mL, respectively.) Patients with severely reduced renal function had elevated mean AUC and Cmax values (98.0 ng/mL*hr and 50.7 ng/mL, respectively), but this study showed only a weak correlation between repaglinide levels and creatinine clearance. Initial dose adjustment does not appear to be necessary for patients with mild to moderate renal dysfunction.However, patients with type 2 diabetes who have severe renal function impairment should initiate PRANDIN therapy with the 0.5 mg dosesubsequently, patients should be carefully titrated. Studies were not conducted in patients with creatinine clearances below 20 mL/min or patients with renal failure requiring hemodialysis.
Hepatic Insufficiency:PRANDIN should be used cautiously in patients with impaired liver function. Longer intervals between dose adjustments should be utilized to allow full assessment of response.
Clinical Trials
Monotherapy Trials
A four-week, double-blind, placebo-controlled dose-response trial was conducted in 138 patients with type 2 diabetes using doses ranging from 0.25 to 4 mg taken with each of three meals. PRANDIN therapy resulted in dose-proportional glucose lowering over the full dose range. Plasma insulin levels increased after meals and reverted toward baseline before the next meal. Most of the fasting blood glucose-lowering effect was demonstrated within 1-2 weeks.
In a double-blind, placebo-controlled, 3-month dose titration study, PRANDIN or placebo doses for each patient were increased weekly from 0.25 mg through 0.5, 1, and 2 mg, to a maximum of 4 mg, until a fasting plasma glucose (FPG) level <160 mg/dL was achieved or the maximum dose reached. The dose that achieved the targeted control or the maximum dose was continued to end of study. FPG and 2-hour post-prandial glucose (PPG) increased in patients receiving placebo and decreased in patients treated with repaglinide. Differences between the repaglinide- and placebo-treated groups were -61 mg/dL (FPG) and -104 mg/dL (PPG). The between-group change in HbA1c, which reflects long-term glycemic control, was 1.7% units.
PRANDIN vs. Placebo Treatment: Mean FPG, PPG, and HbA1c Changes from baseline after 3 months of treatment:
*p < 0.05 for between group differenceFPG (mg/dL)PPG (mg/dL)HbA1c (%)PLRPLRPLRBaseline215.3220.2245.2261.78.18.5Change from Baseline (at last visit)30.3-31.0*56.5-47.6*1.1-0.6*FPG = fasting plasma glucose PPG = post-prandial glucose PL = placebo (N=33) R = repaglinide (N=66)Another double-blind, placebo-controlled trial was carried out in 362 patients treated for 24 weeks. The efficacy of 1 and 4 mg preprandial doses was demonstrated by lowerin |
