Pediatric. The pharmacokinetics of glimepiride (1 mg) were evaluated in a single dose study conducted in 30 Type 2 diabetic patients (Male = 7; Female = 23) between ages 10 and 17 years. The mean AUC_(0-last)(338.8±203.1 ng•hr/mL), Cmax (102.4±47.7 ng/mL) and T½(3.1±1.7 hours) were comparable to those previously reported in adults (AUC(0-last) 315.2±95.9 ng•hr/mL, Cmax 103.2±34.3 ng/mL and T½ 5.3±4.1 hours).

Gender. There were no differences be•ween males and females in the pharmacokinetics of glimepiride when adjustment was made for differences in body weight.

Race. No pharmacokinetic studies to assess the effects of race have been performed, but in placebo-controlled studies of AMARYL (glimepiride tablets) in patients with Type 2 diabetes, the antihyperglycemic effect was comparable in whites (n = 536), blacks (n = 63), and Hispanics (n = 63).

Renal Insufficiency. A single-dose, open-label study was conducted in 15 patients with renal impairment. AMARYL (3 mg) was administered to 3 groups of patients with different levels of mean creatinine clearance (CLcr); (Group I, CLcr = 77.7 mL/min, n = 5), (Group II, CLcr = 27.7 mL/min, n = 3), and (Group III, CLcr = 9.4 mL/min, n = 7). AMARYL was found to be well tolerated in all 3 groups. The results showed that glimepiride serum levels decreased as renal function decreased. However, M1 and m² serum levels (mean AUC values) increased 2.3 and 8.6 times from Group I to Group III. The apparent terminal half-life (T½) for glimepiride did not change, while the half-lives for M1 and m² increased as renal function decreased. Mean urinary excretion of M1 plus m² as percent of dose, however, decreased (44.4%, 21.9%, and 9.3% for Groups I to III).

A multiple-dose titration study was also conducted in 16 Type 2 diabetic patients with renal impairment using doses ranging from 1-8 mg daily for 3 months. The results were consistent with those observed after single doses. All patients with a CLcr less than 22 mL/min had adequate control of their glucose levels with a dosage regimen of only 1 mg daily. The results from this study suggested that a starting dose of 1 mg AMARYL may be given to Type 2 diabetic patients with kidney disease, and the dose may be titrated based on fasting blood glucose levels.

Hepatic Insufficiency. No studies were performed in patients with hepatic insufficiency.

Other Populations. There were no important differences in glimepiride metabolism in subjects identified as phenotypically different drug-metabolizers by their metabolism of sparteine. The pharmacokinetics of glimepiride in morbidly obese patients were similar to those in the normal weight group, except for a lower Cmax and AUC. However, since neither Cmax nor AUC values were normalized for body surface area, the lower values of Cmax and AUC for the obese patients were likely the result of their excess weight and not due to a difference in the kinetics of glimepiride.

Drug Interactions. The hypoglycemic action of sulfonylureas may be potentiated by certain drugs, including nonsteroidal anti-inflammatory drugs and other drugs that are highly protein bound, such as salicylates, sulfonamides, chloramphenicol, coumarins, probenecid, monoamine oxidase inhibitors, and beta adrenergic blocking agents. When these drugs are administered to a patient receiving AMARYL, the patient should be observed closely for hypoglycemia. When these drugs are withdrawn from a patient receiving AMARYL, the patient should be observed closely for loss of glycemic control.

Certain drugs tend to produce hyperglycemia and may lead to loss of control. These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, and isoniazid. When these drugs are administered to a patient receiving AMARYL, the patient should be closely observed for loss of control. When these drugs are withdrawn from a patient receiving AMARYL, the patient should be observed closely for hypoglycemia.

Coadministration of aspirin (1 g tid) and AMARYL led to a 34% decrease in the mean glimepiride AUC and, therefore, a 34% increase in the mean CL/f. The mean Cmax had a decrease of 4%. Blood glucose and serum C-peptide concentrations were unaffected and no hypoglycemic symptoms were reported. Pooled data from clinical trials showed no evidence of clinically significant adverse interactions with uncontrolled concurrent administration of aspirin and other salicylates.

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