DESCRIPTION

GLIMIDIET is 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 (C24H34N4O5S) with a molecular weight of 490.62. Glimepiride is a white to yellowish-white, crystalline, odorless to practically odorless powder and is practically insoluble in water.

CLINICAL PHARMACOLOGY

Mechanism of Action Glimepiride primarily lowers blood glucose by stimulating the release of insulin from pancreatic beta cells. Sulfonylureas bind to the sulfonylurea receptor in the pancreatic beta-cell plasma membrane, leading to closure of the ATP-sensitive potassium channel, thereby stimulating the release of insulin.

INDICATIONS AND USAGE

GLIMIDIET is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus .

Limitations of Use

GLIMIDIET should not be used for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis, as it would not be effective in these settings.

DOSAGE AND ADMINISTRATION

 Recommended Dosing GLIMIDIET should be administered with breakfast or the first main meal of the day. The recommended starting dose of GLIMIDIET is 1 mg or 2 mg once daily. Patients at increased risk for hypoglycemia (e.g., the elderly or patients with renal impairment) should be started on 1 mg once daily. After reaching a daily dose of 2 mg, further dose increases can be made in increments of 1 mg or 2 mg based upon the patient’s glycemic response. Uptitration should not occur more frequently than every 1 to 2 weeks. A conservative titration scheme is recommended for patients at increased risk for hypoglycaemia. The maximum recommended dose is 8 mg once daily. Patients being transferred to GLIMIDIET from longer half-life sulfonylureas (e.g., chlorpropamide) may have overlapping drug effect for 1 to 2 weeks and should be appropriately monitored for hypoglycemia.

DOSAGE FORMS AND STRENGTHS

 GLIMIDIET is formulated as tablets of: 1 mg &   2 mg

CONTRAINDICATIONS

GLIMIDIET is contraindicated in patients with a history of a hypersensitivity reaction to: Glimepiride or any of the product’s ingredients.

WARNINGS AND PRECAUTIONS

Hypoglycemia - All sulfonylureas, including GLIMIDIET, can cause severe hypoglycemia. The patient’s ability to concentrate and react may be impaired as a result of hypoglycemia. These impairments may present a risk in situations where these abilities are especially important, such as driving or operating other machinery. Severe hypoglycemia can lead to unconsciousness or convulsions and may result in temporary or permanent impairment of brain function or death. Patients must be educated to recognize and manage hypoglycemia. Use caution when initiating and increasing GLIMIDIET doses in patients who may be predisposed to hypoglycemia (e.g., the elderly, patients with renal impairment, patients on other anti-diabetic medications). Debilitated or malnourished patients, and those with adrenal, pituitary, or hepatic impairment are particularly susceptible to the hypoglycemic action of glucose-lowering medications. Hypoglycemia is also more likely to occur when caloric intake is deficient, after severe or prolonged exercise, or when alcohol is ingested. Early warning symptoms of hypoglycemia may be different or less pronounced in patients with autonomic neuropathy, the elderly, and in patients who are taking beta-adrenergic blocking medications or other sympatholytic agents. These situations may result in severe hypoglycemia before the patient is aware of the hypoglycemia.

ADVERSE REACTIONS

• Hypoglycemia

 • Hemolytic anemia

DRUG INTERACTIONS

 Drugs Affecting Glucose Metabolism-  A number of medications affect glucose metabolism and may require GLIMIDIET dose adjustment and particularly close monitoring for hypoglycemia or worsening glycemic control.

The following are examples of medications that may increase the glucose-lowering effect of sulfonylureas including GLIMIDIET, increasing the susceptibility to and/or intensity of hypoglycemia: oral anti-diabetic medications, pramlintide acetate, insulin, angiotensin converting enzyme (ACE) inhibitors, H2 receptor antagonists, fibrates, propoxyphene, pentoxifylline, somatostatin analogs, anabolic steroids and androgens, cyclophosphamide, phenyramidol, guanethidine, fluconazole, sulfinpyrazone, tetracyclines, clarithromycin, disopyramide, quinolones, and those drugs that are highly protein-bound, such as fluoxetine, nonsteroidal anti-inflammatory drugs, salicylates, sulfonamides, chloramphenicol, coumarins, probenecid and monoamine oxidase inhibitors.

When these medications are administered to a patient receiving GLIMIDIET, monitor the patient closely for hypoglycemia. When these medications are withdrawn from a patient receiving GLIMIDIET, monitor the patient closely for worsening glycemic control.

The following are examples of medications that may reduce the glucose-lowering effect of sulfonylureas including GLIMIDIET, leading to worsening glycemic control: danazol, glucagon, somatropin, protease inhibitors, atypical antipsychotic medications (e.g., olanzapine and clozapine), barbiturates, diazoxide, laxatives, rifampin, thiazides and other diuretics, corticosteroids, phenothiazines, thyroid hormones, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics (e.g., epinephrine, albuterol, terbutaline), and isoniazid.

When these medications are administered to a patient receiving GLIMIDIET, monitor the patient closely for worsening glycemic control. When these medications are withdrawn from a patient receiving GLIMIDIET, monitor the patient closely for hypoglycemia. Beta-blockers, clonidine, and reserpine may lead to either potentiation or weakening of GLIMIDIET glucose-lowering effect. Both acute and chronic alcohol intake may potentiate or weaken the glucose-lowering action of GLIMIDIET in an unpredictable fashion. The signs of hypoglycemia may be reduced or absent in patients taking sympatholytic drugs such as beta-blockers, clonidine, guanethidine, and reserpine.

 Miconazole A potential interaction between oral miconazole and sulfonylureas leading to severe hypoglycemia has been reported. Whether this interaction also occurs with other dosage forms of miconazole is not known.

 USE IN SPECIFIC POPULATIONS

Pregnancy Risk Summary Available data from a small number of published studies. Use in pregnancy have not identified any drug associated risks for major birth defects, miscarriage, or adverse maternal outcomes. However, sulfonylureas (including glimepiride) cross the placenta and have been associated with neonatal adverse reactions such as hypoglycemia. Therefore, GLIMIDIET should be discontinued at least two weeks before expected delivery. Poorly controlled diabetes in pregnancy is also associated with risks to the mother and fetus  In animal studies, there were no effects on embryo-fetal development following administration of glimepiride to pregnant rats and rabbits at oral doses approximately 4000 times and 60 times the maximum human dose based on body surface area, respectively. However, fetotoxicity was observed in rats and rabbits at doses 50 times and 0.1 times the maximum human dose, respectively.

 Lactation Risk Summary Breastfed infants of lactating women using GLIMIDIET should be monitored for symptoms of hypoglycemia. It is not known whether glimepiride is excreted in human milk and there are no data on the effects of glimepiride on milk production. Glimepiride is present in rat milk . The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for GLIMIDIET and any potential adverse effects on the breastfed child from GLIMIDIET or from the underlying maternal condition. Clinical Considerations Monitoring for adverse reactions Monitor breastfed infants for signs of hypoglycemia (e.g., jitters, cyanosis, apnea, hypothermia, excessive sleepiness, poor feeding, seizures).

PAEDIATRIC USE-

GLIMIDIET is not recommended in pediatric patients because of its adverse effects on body weight and hypoglycemia.

OVERDOSAGE

An overdosage of GLIMIDIET, 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