Amaryl

Approved Indications:

• Type 2 Diabetes Mellitus:
• As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
• Can be used as monotherapy or in combination with other antidiabetic agents, including insulin.

Off-label/Clinically Accepted Uses:

• Occasionally used in early type 2 diabetes where diet control alone is insufficient.
• Sometimes combined with other oral hypoglycemic agents to optimize blood glucose control.

• Adults:
• Initial dose: 1 mg orally once daily with breakfast or the first main meal.
• Maintenance dose: Typically 1–4 mg daily; may be increased to a maximum of 8 mg daily based on glycemic response.
• Dose adjustments should be made at intervals of 1–2 weeks.
• Elderly:
• Start at the lower end of the dosing range and adjust cautiously due to increased risk of hypoglycemia.
• Pediatrics:
• Safety and efficacy not established; use generally not recommended.
• Renal Impairment:
• Use with caution; start at low dose and monitor closely, especially in severe impairment.
• Hepatic Impairment:
• Use cautiously; no specific dosage adjustment recommended but monitor for hypoglycemia.
• Administration Route:
• Oral tablets, taken once daily with food to reduce gastrointestinal side effects and risk of hypoglycemia.

Glimepiride is a second-generation sulfonylurea that stimulates insulin secretion from pancreatic beta cells. It binds to the sulfonylurea receptor (SUR1) on ATP-sensitive potassium channels, causing closure of these channels. This leads to membrane depolarization, opening of voltage-gated calcium channels, increased intracellular calcium, and subsequent insulin release. This enhanced insulin secretion lowers blood glucose levels. Additionally, glimepiride may improve peripheral insulin sensitivity and reduce hepatic glucose output, contributing to its antihyperglycemic effect.

• Absorption: Rapid and nearly complete after oral administration; peak plasma concentration within 2–3 hours.
• Bioavailability: Approximately 100%.
• Distribution: High plasma protein binding (~99.5%).
• Metabolism: Primarily metabolized in the liver by CYP2C9 to inactive metabolites.
• Elimination Half-life: Approximately 5–9 hours.
• Excretion: Metabolites excreted mainly via urine (60%) and feces (40%).

• Pregnancy:
• FDA Category C: Risk cannot be ruled out; use only if clearly needed and benefits justify risks. Insulin is preferred for glycemic control during pregnancy.
• Lactation:
• Excreted in breast milk; caution advised. Alternatives such as insulin preferred during breastfeeding.

• Primary Therapeutic Class: Antidiabetic agent
• Subclass: Sulfonylurea (Second generation)

• Known hypersensitivity to glimepiride or other sulfonylureas or sulfonamides.
• Type 1 diabetes mellitus or diabetic ketoacidosis (with or without coma).
• Severe hepatic impairment.
• Severe renal impairment requiring dialysis.
• Pregnancy and lactation unless benefits outweigh risks.

• Hypoglycemia: Most serious adverse effect; increased risk in elderly, renal/hepatic impairment, or with concomitant insulin or other hypoglycemics.
• Hepatic Dysfunction: Use cautiously; monitor liver function.
• Renal Impairment: Dose reduction and careful monitoring necessary.
• Cardiovascular Risk: Sulfonylureas may increase risk of cardiovascular events; monitor closely.
• Allergic Reactions: Rare but may occur; discontinue if severe rash or hypersensitivity.
• Elderly: Increased susceptibility to hypoglycemia.

Common Adverse Effects:

• Hypoglycemia (mild to severe)
• Dizziness, headache
• Gastrointestinal disturbances: nausea, vomiting, abdominal discomfort
• Weight gain

Serious/Rare Side Effects:

• Severe hypoglycemia (potentially life-threatening)
• Allergic skin reactions (rash, pruritus)
• Hematologic effects (rare leukopenia, thrombocytopenia)
• Hepatic dysfunction (rare)

• Drugs increasing hypoglycemia risk:
• Other antidiabetics, insulin, NSAIDs, warfarin, sulfonamides, fluconazole, beta-blockers (mask hypoglycemia symptoms).
• Drugs reducing glimepiride efficacy:
• Rifampin, phenytoin, carbamazepine, phenobarbital, corticosteroids.
• Enzyme System:
• Metabolized by CYP2C9; inhibitors or inducers of this enzyme can alter glimepiride levels.

• Emphasis on cautious use in elderly and patients with renal or hepatic impairment due to hypoglycemia risk.
• Guidelines favor individualized therapy; consideration of newer antidiabetic agents with lower hypoglycemia risk in combination or as alternatives.
• Recent updates recommend monitoring for cardiovascular risks and encourage patient education on hypoglycemia signs.

• Store at 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep tablets in original container tightly closed.
• Do not freeze.