Glibenil Tablets

Indications

• Type 2 diabetes mellitus
• Non-insulin dependent diabetes

Dosage

Adults: Refer to BNF for specific dosing guidance. Generally, the initial dose may range from 2.5 mg to 5 mg once daily, with possible adjustments based on blood glucose levels and individual patient response.

Mechanism of action

Glibenclamide works by binding to the sulfonylurea receptor (SUR1) on the pancreatic beta-cell membrane, which is part of the ATP-sensitive potassium (K_ATP) channel complex. This binding leads to the closure of the K_ATP channels, resulting in depolarization of the beta cell membrane. The depolarization triggers the opening of voltage-gated calcium channels, leading to an influx of calcium ions. The increased intracellular calcium concentration promotes the exocytosis of insulin granules, thereby enhancing insulin secretion in response to glucose.

Pharmacodynamics

The pharmacodynamic effects of glibenclamide include a reduction in blood glucose levels through increased insulin secretion. The drug also has effects on insulin sensitivity and may contribute to a reduction in hepatic glucose production. Its onset of action is typically within 1-2 hours after oral administration, with peak effects occurring approximately 2-4 hours post-dose. The duration of action can last up to 24 hours, allowing for once or twice daily dosing in most patients.

Pharmacokinetics

Glibenclamide is well absorbed from the gastrointestinal tract, with peak plasma concentrations occurring within 1-3 hours after oral intake. It is highly protein-bound (approximately 99%) and undergoes hepatic metabolism, primarily by cytochrome P450 enzymes. The elimination half-life ranges from 4 to 10 hours, and the drug is predominantly excreted in the urine as metabolites. Renal impairment can affect the clearance of glibenclamide, necessitating dose adjustments in patients with compromised renal function.

Contra-indications

• Hypersensitivity to glibenclamide or any of its components
• Diabetic ketoacidosis
• Type 1 diabetes mellitus
• Severe hepatic impairment
• Severe renal impairment

Adverse effects

• Hypoglycemia
• Weight gain
• Gastrointestinal disturbances (nausea, vomiting, diarrhea)
• Allergic skin reactions (rash, pruritus)
• Hematological effects (leukopenia, thrombocytopenia)
• Liver function abnormalities
• Cardiovascular events (rare)

Interactions

• Other antidiabetic agents (may increase hypoglycemic effect)
• NSAIDs (may enhance hypoglycemia)
• Beta-blockers (may mask symptoms of hypoglycemia)
• Corticosteroids (may increase blood glucose levels)
• Alcohol (may potentiate hypoglycemia or cause disulfiram-like reaction)
• Certain antibiotics (e.g., sulfonamides, may increase hypoglycemic effects)

Precautions

• Assess renal and hepatic function before initiation
• Monitor blood glucose levels regularly
• Use with caution in elderly patients
• Consider dietary habits and adherence to therapy
• Be aware of potential for hypoglycemia, especially in patients with irregular meal patterns

Pregnancy

Glibenclamide is not recommended during pregnancy as it may pose risks to the fetus. Insulin is generally preferred for managing diabetes in pregnant women.

Breast-feeding

Glibenclamide may pass into breast milk. Caution is advised when administering to breastfeeding women, and monitoring of the infant's blood glucose levels may be necessary.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Tablets (various strengths)