Pharmacotherapeutic Group Antidiabetic Agent, Sulfonylurea.
Pharmacology: Pharmacodynamics/kinetics: Onset of action: Peak effect: Blood glucose reductions: 2-3 hours.
Duration: 24 hours.
Absorption: 100%; delayed when given with food.
Distribution: Vd: 8.8 L
Protein binding: >99.5%
Metabolism: Hepatic oxidation via CYP2C9 to M1 metabolite (~33% activity of parent compound); further oxidative metabolism to inactivate M2 metabolite.
Half-life elimination: 5-9 hours.
Time to peak, plasma: 2-3 hours.
Excretion: Urine (60%, 80% to 90% as M1 and M2); feces (40%, 70% as M1 and M2).
Management of type 2 diabetes mellitus (noninsulin dependent, NIDDM) as an adjunct to diet and exercise to lower blood glucose; may be used in combination with metformin or insulin in patients whose hyperglycemia cannot be controlled by diet and exercise in conjunction with a single oral hypoglycemic agent.
Children 10-18 year (unlabeled use): Initial: 1 mg once daily; maintenance: 1-4 mg once daily.
Adults: Initial: 1-2 mg once daily, administered with breakfast or the first main meal; usual maintenance dose: 1-4 mg once daily; after a dose of 2 mg once daily, increase in increments of 2 mg at 1- to 2 week intervals based upon the patient's blood glucose response to a maximum of 8 mg once daily. If inadequate response to maximal dose, combination therapy with metformin may be considered.
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): Initial recommended dose: 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.
Conversion from therapy with long half-life agents: Observe patient carefully for 1-2 weeks when converting from a longer half-life agent (eg, chlorpropamide) to glimepiride due to overlapping hypoglycemic effects.
Dosing adjustment/comments in renal impairment: Clcr <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.
Elderly: Initial: 1 mg/day; dose titration and maintenance dosing should be conservative to avoid hypoglycemia.
Dietary Considerations Administer with breakfast or the first main meal of the day. Dietary modification based on ADA recommendations is a part of therapy. Decreases blood glucose concentration. Hypoglycemia may occur. Must be able to recognize symptoms of hypoglycemia (palpitations, sweaty palms, lightheadedness).
Monitoring Parameters: Urine for glucose and ketones; monitor for signs and symptoms of hypoglycemia (fatigue, excessive hunger, profuse sweating, numbness of extremities), fasting blood glucose, hemoglobin A1c, fructosamine.
Reference Range Target range: Adults: Fasting blood glucose: <120 mg/dL. Glycosylated hemoglobin: <7%.
Administration: Administer once daily with breakfast or first main meal of the day. Patients who are NPO may need to have their dose held to avoid hypoglycemia.
Symptoms include low blood sugar, tingling of lips and tongue, nausea, yawning, confusion, agitation, tachycardia, sweating, convulsions, stupor and coma. Intoxication with sulfonylureas can cause hypoglycemia and are best managed with glucose administration (orally for milder hypoglycemia or by injection in more severe forms). Patients should be monitored for a minimum of 24-48 hours after ingestion.
Hypersensitivity to glimepiride, any component of the formulation, or 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 ethanol is ingested, or when more than one glucose-lowering drug is used. It is more likely in elderly patients, malnourished patients and in patients with impaired renal or hepatic function; use with caution.
Chemical similarities are present among sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides, and loop diuretics (except ethacrynic acid). Use in patients with sulfonamide allergy is specifically contraindicated in product labeling, however, a risk of cross-reaction exists in patients with allergy to any of these compounds; avoid use when previous reaction has been severe.
Product labeling states oral hypoglycemic drugs may be associated with an increased cardiovascular mortality as compared to treatment with diet alone or diet plus insulin. Data to support this association are limited, and several studies, including a large prospective trial (UKPDS) have not supported an association.
It may be necessary to discontinue therapy and administer insulin if the patient is exposed to stress (fever, trauma, infection, surgery). Safety and efficacy have not been established in children.
Pregnancy: Pregnancy Risk Factor: C.
Abnormal blood glucose levels are associated with a higher incidence of congenital abnormalities. Insulin is the drug of choice for the control of diabetes mellitus during pregnancy.
Lactation: It is unknown whether this product is excreted in the breast milk. It is not recommended for use in lactating women.
1% to 10%: Central nervous system:
Dizziness (2%), headache (2%).
Endocrine and metabolic: Hypoglycemia (1% to 2%). Gastrointestinal: Nausea (1%).
Neuromuscular and skeletal: Weakness (2%).
<1% or frequency not defined: Agranulocytosis, anorexia, aplastic anemia, cholestatic jaundice, constipation, diarrhea, disulfiram-like reaction, diuretic effect, edema, epigastric fullness, gastrointestinal pain, erythema, heartburn, hemolytic anemia, hepatitis, hypoglycemia, hyponatremia, leukopenia, liver function tests abnormal, nausea, pancytopenia, photosensitivity, porphyria cutanea tarda, pruritus, rash (morbilliform or maculopapular), SIADH, thrombocytopenia, urticaria, vasculitis (allergic), visual accommodation changes (early treatment), vomiting.
Cytochrome P450 Effect: Substrate of CYP2C9 (major).
Increased Effect/Toxicity: CYP2C9 inhibitors may increase the levels/effects of glimepiride; example inhibitors include delavirdine, ketoconazole, nicardipine, NSAIDs, and pioglitazone.
Beta-blockers, chloramphenicol, cimetidine, clofibrate, fluconazole, gemfibrozil, pegvisomant, salicylates, sulfonamides, and tricyclic antidepressants may increase the hypoglycemic effects of glimepiride. Glimepiride may increase effects of coumarins and cyclosporine. Sulfonylureas may induce a disulfiram-like reaction.
Decreased Effect: CYP2C9 inducers may decrease the levels/effects of glimepiride; example inducers include carbamazepine, phenobarbital, phenytoin, rifampin, rifapentine, and secobarbital. There may be a decreased effect of glimepiride with corticosteroids, estrogens, oral contraceptives, thiazide and other diuretics, phenothiazines, NSAIDs, thyroid products, nicotinic acid, isoniazid, sympathomimetics, urinary alkalinizers, and charcoal.
Note: However, pooled data did not demonstrate drug interactions with calcium channel blockers, estrogens, NSAIDs, HMG-CoA reductase inhibitors, sulfonamides, or thyroid hormone.
Ethanol/Nutrition/Herb Interactions: Ethanol: Caution with ethanol (may cause hypoglycemia).
Herb/Nutraceutical: Caution with chromium, garlic, gymnema (may cause hypoglycemia).
A10BB12 - glimepiride ; Belongs to the class of sulfonylureas. Used in the treatment of diabetes.
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