Glimepiride
Pronouncation: (glye-MEP-i-ride)
Class: Sulfonylurea
Trade Names:
Amaryl
- Tablets 1 mg
- Tablets 2 mg
- Tablets 4 mg
Mechanism of Action
Pharmacology
Decreases blood glucose by stimulating insulin release from pancreas. May also decrease hepatic glucose production as well as increase sensitivity to insulin.
Pharmacokinetics
Absorption
Bioavailability is 100%. C max is about 103 to 591 ng/mL (dose-dependent). T max is about 2 to 3 h.
Food
T max increased and C max and AUC slightly decreased.
Distribution
Vd is 8.8 L. Protein binding is greater than 99.5%.
Metabolism
Completely metabolized by oxidation via CYP-450 2C9. Major metabolites are cyclohexylhydroxymethyl (M1) (about 1/ 3 of the activity of the parent) and carboxyl (M2) derivatives.
Elimination
About 60% is excreted in urine and about 40% in feces as metabolites. The t ½ is about 5 to 9.2 h.
Peak
2 to 3 h.
Duration
24 h.
Special Populations
Renal Function Impairment
Serum levels decrease, M1 and M2 levels increase, and t ½ for M1 and M2 increase.
Elderly
Mean AUC was about 13% lower.
Indications and Usage
Adjunct to diet and exercise in patients with type 2 diabetes whose hyperglycemia cannot be controlled by diet and exercise alone; in combination with metformin when diet, exercise, and glimepiride or metformin alone do not result in adequate glycemic control; in combination with insulin in patients whose hyperglycemia cannot be controlled by diet and exercise in conjunction with an oral hypoglycemic agent.
Contraindications
Hypersensitivity to sulfonylureas; diabetic ketoacidosis with or without coma.
Dosage and Administration
Adults
PO 1 to 2 mg daily with breakfast or the first main meal of the day. Increase by 1 to 2 mg/dose. Titrate at 1- to 2-wk intervals based on blood glucose response.
Maintenance
1 and 4 mg daily (max, 8 mg/day). Combination therapy with insulin is appropriate for secondary failure to oral sulfonylureas. The same dosing recommendations apply.
In Combination With Metformin
Adults
PO Obtain desired control of blood glucose by adjusting the dose of each drug; however, make attempts to determine the minimum effective dose of each drug.
In Combination With Insulin
Adults
PO The fasting glucose level for instituting combination therapy is greater than 150 mg/dL. The recommended glimepiride dose is 8 mg once daily with the first main meal. Start with low-dose insulin and adjust the insulin dose weekly, as guided by fasting blood glucose. Once stabilized, monitor capillary blood glucose daily. Periodic adjustments in insulin may be necessary, as determined by glucose and glycosylated hemoglobin levels.
Storage/Stability
Store between 59° and 86°F.
Drug Interactions
ACE inhibitors, beta-blockers, chloramphenicol, clofibrate, diazoxide, fenfluramine, histamine H 2 antagonists, MAOIs, miconazole, NSAIDs, probenecid, quinolones (eg, ciprofloxacin), salicylates, sulfinpyrazone, sulfonamides, tricyclic antidepressants, urinary acidifiers
May increase hypoglycemic effect.
Alcohol
Produces disulfiram-like reaction (eg, breathlessness, facial flushing, headache).
Corticosteroids, estrogens, isoniazid, nicotinic acid, oral contraceptives, phenothiazines, phenytoin, sympathomimetics, thiazide and other diuretics, thyroid products
These agents may produce hyperglycemia, leading to loss of glycemic control.
Fluconazole, fluvastatin, fluvoxamine, gemfibrozil, ketoconazole
May elevate glimepiride blood levels, increasing the risk of hypoglycemia.
Rifamycins
Glimepiride blood levels may be decreased, increasing the risk of hyperglycemia.
Laboratory Test Interactions
None well documented.
Adverse Reactions
CNS
Asthenia, dizziness, headache (2%).
GI
Nausea (1%).
Hematologic-Lymphatic
Agranulocytosis, aplastic anemia, hemolytic anemia, leukopenia, pancytopenia, thrombocytopenia.
Precautions
Monitor
Monitor fasting blood glucose to determine therapeutic response, monitor glycosylated hemoglobin every 3 to 6 mo.
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Pregnancy
Category C . Insulin is recommended to maintain blood glucose levels during pregnancy. Prolonged severe neonatal hypoglycemia can occur if sulfonylureas are administered at time of delivery.
Lactation
Undetermined.
Children
Safety and efficacy not established.
Elderly
Increased risk for development of hypoglycemia. Hypoglycemia may be difficult to detect in elderly patients.
Renal Function
Use with caution; lower doses may be adequate.
Hepatic Function
Use with caution; lower doses may be adequate.
CV
Oral hypoglycemic agents have been associated with an increase in CV mortality compared with diet alone or diet plus insulin.
Overdosage
Symptoms
Coma, confusion, convulsions, hunger, hypoglycemia, lethargy, nausea, stupor, sweating, tachycardia, tingling of lips and tongue, tremor.
Patient Information
- Instruct patient in signs, symptoms, and treatment of hypoglycemic reaction.
- Review dietary and exercise guidelines for diabetes with patient.
- Instruct patient to take drug with breakfast.
- Teach patient to self-monitor urine or blood glucose.
- Instruct patients to inform all health care providers that they are taking this drug and to carry medical identification (eg, card, bracelet).
- Instruct patient to notify health care provider if symptoms of hypoglycemia occur (eg, excessive hunger, fatigue, numbness of extremities, profuse sweating) or if blood glucose is below 60 mg/dL.
- Tell patient to notify health care provider if symptoms of hyperglycemia occur (eg, excessive thirst or urination, urinary glucose or ketones).
- Instruct patient to report the following symptoms to health care provider: diarrhea, heartburn, nausea, rash, sore throat, unusual bleeding or bruising, vomiting, or any other adverse reactions.
- Advise patient to avoid exposure to sunlight or sunlamps and to use sunscreen or wear protective clothing to avoid photosensitivity reaction.
- Advise patient to check with health care provider before drinking alcohol.
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