No

Antidiabetic Agent (Sulfonylurea)

Management of noninsulin-dependent diabetes mellitus (type 2) as an adjunct to diet and exercise to lower blood glucose

Use in combination with insulin to lower blood glucose in patients whose hyperglycemia cannot be controlled by diet and exercise in conjunction with an oral hypoglycemic agent

C

Hypersensitivity to glimepiride or any component, other sulfonamides; diabetic ketoacidosis (with or without coma)

All sulfonylurea drugs are capable of producing severe hypoglycemia. 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.

The administration of oral hypoglycemic drugs has been reported to be associated with increased cardiovascular mortality as compared to treatment with diet alone or diet plus insulin

At higher dosages, sulfonylureas may block the ATP-sensitive potassium channels, which may correspond to an increased risk of cardiovascular events. In May, 2000, the National Diabetes Center issued a warning to avoid the use of sulfonylureas at higher dosages (glimepiride daily doses >1 mg).

1% to 10%: Central nervous system: Headache

<1%: Edema, rash, urticaria, photosensitivity, hypoglycemia, hyponatremia, anorexia, nausea, vomiting, diarrhea, epigastric fullness, constipation, heartburn, blood dyscrasias, aplastic anemia, hemolytic anemia, bone marrow suppression, thrombocytopenia, agranulocytosis, cholestatic jaundice, diuretic effect

Symptoms of overdose include low blood sugar, tingling of lips and tongue, nausea, yawning, confusion, agitation, tachycardia, sweating, convulsions, stupor, and coma

Intoxications with sulfonylureas can cause hypoglycemia and are best managed with glucose administration (oral for milder hypoglycemia or by injection in more severe forms). Patients should be monitored for a minimum of 24-48 hours after ingestion.

CYP2C9 enzyme substrate

Increased effects: H₂-antagonists, anticoagulants, androgens, beta-blockers, fluconazole, salicylates, gemfibrozil, sulfonamides, tricyclic antidepressants, probenecid, MAO inhibitors, methyldopa, NSAIDs, salicylates, sulfonamides, chloramphenicol, coumarins, probenecid, MAO inhibitors, digitalis glycosides, urinary acidifiers

Increased toxicity: Cimetidine may increase hypoglycemic effects; 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.

Stimulates insulin release from the pancreatic beta cells; reduces glucose output from the liver; insulin sensitivity is increased at peripheral target sites

Duration of action: 24 hours

Peak blood glucose reductions: Within 2-3 hours

Protein binding: >99.5%

Absorption: 100% absorbed; delayed when given with food

Metabolism: Completely in the liver

Half-life: 5-9 hours

Elimination: Metabolites excreted in urine and feces

Oral (allow several days between dose titrations):

Elderly: Initial: 1 mg/day

Combination with insulin therapy (fasting glucose level for instituting combination therapy is in the range of >150 mg/dL in plasma or serum depending on the patient): 8 mg once daily with the first main meal

After starting with low-dose insulin, upward adjustments of insulin can be done approximately weekly as guided by frequent measurements of fasting blood glucose. Once stable, combination-therapy patients should monitor their capillary blood glucose on an ongoing basis, preferably daily.

At higher dosages, sulfonylureas may block the ATP-sensitive potassium channels, which may correspond to an increased risk of cardiovascular events. In May, 2000, the National Diabetes Center issued a warning to avoid the use of sulfonylureas at higher dosages (glimepiride daily doses >1 mg); see Warnings/Precautions.

Dosing adjustment/comments in renal impairment: Cl_cr <22 mL/minute: Initial starting dose should be 1 mg and dosage increments should be based on fasting blood glucose levels

Dosing adjustment in hepatic impairment: No data available

Administer with breakfast or the first main meal of the day

Urine for glucose and ketones; monitor for signs and symptoms of hypoglycemia (fatigue, excessive hunger, profuse sweating, numbness of extremities), fasting blood glucose, hemoglobin A_1c, fructosamine

Target range: Adults:

Glycosylated hemoglobin: <7%

None reported

May rarely cause agranulocytosis; use caution with clozapine and carbamazepine; phenothiazines and TCAs may antagonize glimepiride hypoglycemic effects; MAOIs and TCAs may enhance hypoglycemic effects

No information available to require special precautions

Glimepiride-dependent diabetics (noninsulin dependent, type 2) should be appointed for dental treatment in morning in order to minimize chance of stress-induced hypoglycemia

This medication is used to control diabetes; it is not a cure. Other components of treatment plan are important: follow prescribed diet, medication, and exercise regimen. Take exactly as directed; 30 minutes before meal(s) at the same time each day. Do not change dose or discontinue without consulting prescriber. Avoid alcohol while taking this medication; could cause severe reaction. Inform prescriber of all other prescription or OTC medications you are taking; do not introduce new medication without consulting prescriber. Do not take other medication within 2 hours of this medication unless so advised by prescriber. If you experience hypoglycemic reaction, contact prescriber immediately. Maintain regular dietary intake and exercise routine and always carry quick source of sugar with you. You may experience side effects during first weeks of therapy (headache, nausea); consult prescriber if these persist. Report severe or persistent side effects, extended vomiting or flu-like symptoms, skin rash, easy bruising or bleeding, or change in color of urine or stool. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Do not breast-feed.

Patients who are NPO may need to have their dose held to avoid hypoglycemia

Tablet: 1 mg, 2 mg, 4 mg