What are the side effects of glibenclamide?

Side Effects of Glibenclamide

Glibenclamide (glyburide in the US and Canada) is associated with a substantially greater risk of hypoglycemia than other second-generation sulfonylureas, making it a less preferable choice, especially in elderly patients. 1

Major Side Effects

Hypoglycemia

• Most serious and potentially life-threatening side effect
• Can be prolonged (12-72 hours) and severe 2
• Higher risk in:
  • Elderly patients (median age 75 in reported cases) 2
  • Patients with renal dysfunction 1
  • Patients with previous stroke or cardiac disorders 2
  • First month of treatment (20% of cases) 2

Metabolic Effects

• Weight gain (approximately 2 kg common following initiation) 1
• Hyperlipidemia (25-50% of patients experience increased serum triglycerides) 1
• Risk of atherosclerosis with chronically elevated triglycerides 1

Hepatic Effects

• Elevation in transaminases (13-16% of patients) 1
• Rare cases of toxic hepatitis 1

Less Common Side Effects

Gastrointestinal

• Nausea
• Abdominal discomfort

Allergic Reactions

• Skin rashes
• Photosensitivity

Other Rare Effects

• Bone marrow suppression
• Blood dyscrasias

Drug Interactions

Important Interactions

• Potentiation of glucose-lowering effect when combined with other antidiabetic medications 1
• Drugs that interfere with cytochrome P450 metabolism (e.g., cyclosporine) 1
• Drugs that compete for plasma protein binding (e.g., phenytoin) 1
• Concomitant administration of vitamin A increases risk of hypervitaminosis A 1

Risk Factors for Side Effects

Patient Factors Increasing Risk

• Advanced age (>65 years) 2, 3
• Renal impairment 1, 3
• Hepatic dysfunction
• Cardiac disease 3
• Poor nutritional status or irregular meals 2
• Alcohol consumption 2

Monitoring Recommendations

Laboratory Monitoring

• Regular blood glucose monitoring (especially when initiating therapy)
• Periodic liver function tests
• Lipid profile monitoring
• Renal function tests

Clinical Monitoring

• Signs and symptoms of hypoglycemia (confusion, sweating, tachycardia)
• Weight changes
• Signs of fluid retention

Precautions and Contraindications

Contraindications

• Severe renal impairment
• Severe hepatic impairment
• Pregnancy (due to risk of neonatal hypoglycemia)

Use with Caution

• Elderly patients (consider alternative sulfonylureas) 1, 2
• Patients with cardiac disease 3
• Patients with irregular eating patterns

Management of Side Effects

Hypoglycemia Management

• Immediate administration of glucose
• May require prolonged glucose infusion (up to 60+ hours in severe cases) 3
• Hospital admission for severe cases

Prevention Strategies

• Start with lower doses in high-risk patients
• Regular meals and blood glucose monitoring
• Patient education about hypoglycemia symptoms and management
• Consider alternative medications in high-risk patients

Glibenclamide's mechanism of action involves inhibiting ATP-sensitive potassium channels, leading to cell depolarization and insulin secretion 4. Both the parent compound and its metabolites (4-trans-hydroxy-glibenclamide and 3-cis-hydroxy-glibenclamide) have hypoglycemic effects 5, which explains the prolonged nature of hypoglycemic episodes.