Glimepiride (Page 3 of 6)

8.4 Pediatric Use

The pharmacokinetics, efficacy and safety of glimepiride have been evaluated in pediatric patients with type 2 diabetes as described below. Glimepiride is not recommended in pediatric patients because of its adverse effects on body weight and hypoglycemia.
The pharmacokinetics of a 1 mg single dose of glimepiride was evaluated in 30 patients with type 2 diabetes (male=7; female=23) between ages 10 and 17 years. The mean (± SD) AUC(0-last) (339±203 ng•hr/mL), Cmax (102±48 ng/mL) and t1/2 (3.1±1.7 hours) for glimepiride were comparable to historical data from adults (AUC(0-last) 315±96 ng•hr/mL, Cmax 103±34 ng/mL, and t1/2 5.3±4.1 hours).
The safety and efficacy of glimepiride in pediatric patients was evaluated in a single-blind, 24-week trial that randomized 272 patients (8 to 17 years of age) with type 2 diabetes to glimepiride (n=135) or metformin (n=137). Both treatment-naive patients (those treated with only diet and exercise for at least 2 weeks prior to randomization) and previously treated patients (those previously treated or currently treated with other oral antidiabetic medications for at least 3 months) were eligible to participate. Patients who were receiving oral antidiabetic agents at the time of study entry discontinued these medications before randomization without a washout period. Glimepiride was initiated at 1 mg, and then titrated up to 2, 4, or 8 mg (mean last dose 4 mg) through Week 12, targeting a self-monitored fasting fingerstick blood glucose <126 mg/dL. Metformin was initiated at 500 mg twice daily and titrated at Week 12 up to 1000 mg twice daily (mean last dose 1365 mg).After 24 weeks, the overall mean treatment difference in HbA1c between glimepiride and metformin was 0.2%, favoring metformin (95% confidence interval -0.3% to +0.6%). Based on these results, the trial did not meet its primary objective of showing a similar reduction in HbA1c with glimepiride compared to metformin.

Table 2: Change from Baseline in HbA1C and Body Weight in Pediatric Patients Taking Glimepiride or Metformin
Metformin Glimepiride
* Intent-to-treat population using last-observation-carried-forward for missing data (glimepiride, n=127; metformin, n=126) adjusted for baseline HbA1C and Tanner Stage Difference is glimepiride – metformin with positive differences favoring metformin
Treatment-Naive Patients* N=69 N=72
HbA1C (%)
Baseline (mean) 8.2 8.3
Change from baseline (adjusted LS mean) -1.2 -1
Adjusted Treatment Difference (95%CI) 0.2 (-0.3; 0.6)
Previously Treated Patients* N=57 N=55
HbA1C (%)
Baseline (mean) 9 8.7
Change from baseline (adjusted LS mean) -0.2 0.2
Adjusted Treatment Difference (95%CI) 0.4 (-0.4; 1.2)
Body Weight (kg)* N=126 N=129
Baseline (mean) 67.3 66.5
Change from baseline (adjusted LS mean) 0.7 2
Adjusted Treatment Difference (95% CI) 1.3 (0.3; 2.3)

The profile of adverse reactions in pediatric patients treated with glimepiride was similar to that observed in adults [see Adverse Reactions (6)].Hypoglycemic events documented by blood glucose values <36 mg/dL were observed in 4% of pediatric patients treated with glimepiride and in 1% of pediatric patients treated with metformin. One patient in each treatment group experienced a severe hypoglycemic episode (severity was determined by the investigator based on observed signs and symptoms).

8.5 Geriatric Use

In clinical trials of glimepiride, 1053 of 3491 patients (30%) were >65 years of age. No overall differences in safety or effectiveness were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
There were no significant differences in glimepiride pharmacokinetics between patients with type 2 diabetes ≤65 years (n=49) and those >65 years (n=42) [see Clinical Pharmacology (12.3)].Glimepiride is substantially excreted by the kidney. Elderly patients are more likely to have renal impairment. In addition, hypoglycemia may be difficult to recognize in the elderly [see Dosage and Administration (2.1) and Warnings and Precautions (5.1)]. Use caution when initiating glimepiride and increasing the dose of glimepiride in this patient population.

8.6 Renal Impairment

To minimize the risk of hypoglycemia, the recommended starting dose of glimepiride is 1 mg daily for all patients with type 2 diabetes and renal impairment [see Dosage and Administration (2.1) and Warnings and Precautions (5.1)].A multiple-dose titration study was conducted in 16 patients with type 2 diabetes and renal impairment using doses ranging from 1 mg to 8 mg daily for 3 months. Baseline creatinine clearance ranged from 10 to 60 mL/min. The pharmacokinetics of glimepiride was evaluated in the multiple-dose titration study and the results were consistent with those observed in patients enrolled in a single-dose study. In both studies, the relative total clearance of glimepiride increased when kidney function was impaired. Both studies also demonstrated that the elimination of the two major metabolites was reduced in patients with renal impairment [see Clinical Pharmacology (12.3)].

10 OVERDOSAGE

An overdosage of glimepiride, as with other sulfonylureas, can produce severe hypoglycemia. Mild episodes of hypoglycemia can be treated with oral glucose. Severe hypoglycemic reactions constitute medical emergencies requiring immediate treatment. Severe hypoglycemia with coma, seizure, or neurological impairment can be treated with glucagon or intravenous glucose. Continued observation and additional carbohydrate intake may be necessary because hypoglycemia may recur after apparent clinical recovery [see Warnings and Precautions (5.1)].

11 DESCRIPTION

Glimepiride tablets, USP are an oral sulfonylurea that contains the active ingredient glimepiride. Chemically, glimepiride is identified as 1-[[p-[2-(3-ethyl-4-methyl-2-oxo-3-pyrroline-1-carboxamido)ethyl]phenyl]sulfonyl]-3-(trans-4-methylcyclohexyl)urea (C24 H34 N4 O5 S) with a molecular weight of 490.62. Glimepiride USP is a white or almost white powder and is practically insoluble in water.The structural formula is:

Chemical Structure
(click image for full-size original)

Glimepiride tablets, USP contain the active ingredient glimepiride and the following inactive ingredients: lactose monohydrate, magnesium stearate, microcrystalline cellulose, povidone, and sodium starch glycolate. In addition, 1 mg contains ferric oxide red, 2 mg contains ferric oxide yellow and FD&C blue No. 2, and 4 mg contains FD&C blue No. 2.

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