Glimepiride precautions

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Phone:617-632-7753

List of precautions

General

• Hypoglycemia
• Loss of control of blood glucose
• Decrease in effectiveness

Lab tests

Carcinogenesis

Mutagenesis

Impairment of fertility

Pregnancy

• Teratogenic effects
• Nonteratogenic effects

Nursing mothers

Pediatric use

Geriatric use

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General

Hypoglycemia

All sulfonylurea drugs are capable of producing severe hypoglycemia. Proper patient selection, dosage, and instructions are important to avoid hypoglycemic episodes. Patients with impaired renal function may be more sensitive to the glucose-lowering effect of Glimepiride. A starting dose of 1 mg once daily followed by appropriate dose titration is recommended in those patients. Debilitated or malnourished patients, and those with adrenal, pituitary, or hepatic insufficiency are particularly susceptible to the hypoglycemic action of glucose-lowering drugs. Hypoglycemia may be difficult to recognize in the elderly and in people who are taking beta-adrenergic blocking drugs or other sympatholytic agents. Hypoglycemia is more likely to occur when caloric intake is deficient, after severe or prolonged exercise, when alcohol is ingested, or when more than one glucose-lowering drug is used. Combined use of Glimepiride with insulin or metformin may increase the potential for hypoglycemia. Return to top

Loss of control of blood glucose

When a patient stabilized on any diabetic regimen is exposed to stress such as fever, trauma, infection, or surgery, a loss of control may occur. At such times, it may be necessary to add insulin in combination with Glimepiride or even use insulin monotherapy. Return to top

Decrease in effectiveness

The effectiveness of any oral hypoglycemic drug, including Glimepiride, in lowering blood glucose to a desired level decreases in many patients over a period of time, which may be due to progression of the severity of the diabetes or to diminished responsiveness to the drug. This phenomenon is known as secondary failure, to distinguish it from primary failure in which the drug is ineffective in an individual patient when first given. Should secondary failure occur with Glimepiride or metformin monotherapy, combined therapy with Glimepiride and metformin or Glimepiride and insulin may result in a response. Should secondary failure occur with combined Glimepiride/metformin therapy, it may be necessary to initiate insulin therapy. Return to top

Lab tests

Fasting blood glucose should be monitored periodically to determine therapeutic response. Glycosylated hemoglobin should also be monitored, usually every 3 to 6 months, to more precisely assess long-term glycemic control. Return to top

Carcinogenesis

Studies in rats at doses of up to 5000 ppm in complete feed (approximately 340 times the maximum recommended human dose, based on surface area) for 30 months showed no evidence of carcinogenesis. In mice, administration of Glimepiride for 24 months resulted in an increase in benign pancreatic adenoma formation which was dose related and is thought to be the result of chronic pancreatic stimulation. The no-effect dose for adenoma formation in mice in this study was 320 ppm in complete feed, or 46 to 54 mg/kg body weight/day. This is about 35 times the maximum human recommended dose of 8 mg once daily based on surface area. Return to top

Mutagenesis

Glimepiride was non-mutagenic in a battery of in vitro and in vivo mutagenicity studies (Ames test, somatic cell mutation, chromosomal aberration, unscheduled DNA synthesis, mouse micronucleus test). Return to top

Impairment of fertility

There was no effect of Glimepiride on male mouse fertility in animals exposed up to 2500 mg/kg body weight (> 1,700 times the maximum recommended human dose based on surface area). Glimepiride had no effect on the fertility of male and female rats administered up to 4000 mg/kg body weight (approximately 4,000 times the maximum recommended human dose based on surface area). Return to top

Pregnancy

Pregnancy category C

Teratogenic effects

Glimepiride did not produce teratogenic effects in rats exposed orally up to 4000 mg/kg body weight (approximately 4,000 times the maximum recommended human dose based on surface area) or in rabbits exposed up to 32 mg/kg body weight (approximately 60 times the maximum recommended human dose based on surface area). Glimepiride has been shown to be associated with intrauterine fetal death in rats when given in doses as low as 50 times the human dose based on surface area and in rabbits when given in doses as low as 0.1 times the human dose based on surface area. This fetotoxicity, observed only at doses inducing maternal hypoglycemia, has been similarly noted with other sulfonylureas, and is believed to be directly related to the pharmacologic (hypoglycemic) action of Glimepiride.
There are no adequate and well-controlled studies in pregnant women. On the basis of results from animal studies, Glimepiride tablets should not be used during pregnancy. Because recent information suggests that abnormal blood glucose levels during pregnancy are associated with a higher incidence of congenital abnormalities, many experts recommend that insulin be used during pregnancy to maintain glucose levels as close to normal as possible. Return to top

Nonteratogenic effects

In some studies in rats, offspring of dams exposed to high levels of Glimepiride during pregnancy and lactation developed skeletal deformities consisting of shortening, thickening, and bending of the humerus during the postnatal period. Significant concentrations of Glimepiride were observed in the serum and breast milk of the dams as well as in the serum of the pups. These skeletal deformations were determined to be the result of nursing from mothers exposed to Glimepiride.
Prolonged severe hypoglycemia (4 to 10 days) has been reported in neonates born to mothers who were receiving a sulfonylurea drug at the time of delivery. This has been reported more frequently with the use of agents with prolonged half-lives. Patients who are planning a pregnancy should consult their physician, and it is recommended that they change over to insulin for the entire course of pregnancy and lactation. Return to top

Nursing mothers

In rat reproduction studies, significant concentrations of Glimepiride were observed in the serum and breast milk of the dams, as well as in the serum of the pups. Although it is not known whether Glimepiride is excreted in human milk, other sulfonylureas are excreted in human milk. Because the potential for hypoglycemia in nursing infants may exist, and because of the effects on nursing animals, Glimepiride should be discontinued in nursing mothers. If Glimepiride is discontinued, and if diet and exercise alone are inadequate for controlling blood glucose, insulin therapy should be considered. Return to top

Pediatric use

The safety and efficacy of Glimepiride were evaluated in an active-controlled, single-blind (patients only), 24-week trial involving 272 pediatric patients, ranging from 8 to 17 years of age, with Type 2 diabetes. Glimepiride (n = 135) was administered at 1mg initially, and then titrated up to 2, 4 or 8 mg (mean last dose 4 mg) until the therapeutic goal of self-monitored fasting blood glucose < 7 mmol/L (< 126 mg/dl) was achieved. The active comparator metformin (n = 137) was administered at 500 mg twice daily initially and titrated up to 1000 mg twice daily (mean last dose 1469 mg).
The profile of adverse reactions in pediatric patients treated with Glimepiride was similar to that observed in adults.
Hypoglycemic events, as documented by blood glucose values < 36 mg/dL, were observed in 4% of patients treated with Glimepiride and in 1% of patients treated with metformin. Return to top

Geriatric use

In US clinical studies of Glimepiride, 608 of 1986 patients were 65 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, but greater sensitivity of some older individuals cannot be ruled out.
Comparison of Glimepiride pharmacokinetics in Type 2 diabetic patients ≤ 65 years (n = 49) and those > 65 years (n = 42) was performed in a study using a dosing regimen of 6 mg daily. There were no significant differences in Glimepiride pharmacokinetics between the two age groups.
The drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
Elderly patients are particularly susceptible to hypoglycemic action of glucose-lowering drugs. In elderly, debilitated, or malnourished patients, or in patients with renal and hepatic insufficiency, the initial dosing, dose increments, and maintenance dosage should be conservative based upon blood glucose levels prior to and after initiation of treatment to avoid hypoglycemic reactions. Hypoglycemia may be difficult to recognize in the elderly and in people who are taking beta-adrenergic blocking drugs or other sympatholytic agents. Return to top

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The content of this page is taken from the FDA package insert for this drug and should not be edited.