Glibenclamide
Regulatory sources consulted
- AEMPS CIMA: https://cima.aemps.es/cima/dochtml/ft/50337/FT_50337.html
- ANSM BDPM: https://base-donnees-publique.medicaments.gouv.fr/affichageDoc.php?specid=69352192&typedoc=R
- EMA EPAR Amglidia: https://www.ema.europa.eu/en/medicines/human/EPAR/amglidia
- AEMPS CIMA · nº registro 50337 ↗
- ANSM BDPM · CIS 69352192 ↗
- EMA EPAR · EMEA/H/C/004379 ↗
Approved indications
- Type 2 diabetes mellitus in adults, when diet, physical exercise, and weight reduction alone are not adequate to control blood glucose.
- Treatment of neonatal diabetes mellitus, for use in newborns, infants and children. It has been shown to be effective in patients with mutations in the genes coding for the β-cell ATP-sensitive potassium channel and chromosome 6q24-related transient neonatal diabetes mellitus.
Contraindications
Absolute
- Hypersensitivity to glibenclamide, other sulfonylureas, or excipients.
- Type 1 diabetes, diabetic ketoacidosis, diabetic pre-coma.
- Severe renal or hepatic impairment.
- Concomitant treatment with miconazole.
- Porphyria.
- Breast-feeding.
Clinical warnings
- Major warning · Hypoglycemia: Increased risk of hypoglycemia, which can be severe and prolonged. Requires careful patient selection, dosage, and patient education. — ANSM SPC
- G6PD deficiency: Risk of hemolytic anemia. A therapeutic alternative is recommended. — ANSM SPC
- Cardiovascular mortality: Epidemiological studies suggest that the use of glibenclamide is associated with an increased risk of cardiovascular mortality compared to treatment with metformin or gliclazide. — ANSM SPC
Drug interactions
- HighMiconazole (systemic, oral gel)J02AB01
Mechanism: Strong inhibition of glibenclamide metabolism (CYP2C9), which drastically increases plasma concentrations and the risk of severe, life-threatening hypoglycemia.
Recommendation: Association is contraindicated.
ANSM SPC
- ModerateFluconazoleJ02AC01
Mechanism: Inhibition of CYP2C9, increasing the half-life of glibenclamide and the risk of hypoglycemia.
Recommendation: Reinforce blood glucose self-monitoring. Consider adjusting the glibenclamide dose during and after treatment with fluconazole.
ANSM SPC
- ModerateBeta-blockersC07
Mechanism: Mask adrenergic symptoms of hypoglycemia (e.g., tachycardia, palpitations). Non-cardioselective beta-blockers may also increase the incidence and severity of hypoglycemia.
Recommendation: Warn the patient about the masking of symptoms and the need for stricter blood glucose monitoring, especially at the start of treatment.
ANSM SPC
- ModerateBosentanC02KX01
Mechanism: Bosentan is an inducer of CYP2C9 and CYP3A4, which may decrease plasma concentrations and efficacy of glibenclamide. Hepatotoxicity has been reported with the combination.
Recommendation: Avoid co-administration. If necessary, closely monitor blood glucose and liver function.
ANSM SPC
Adverse events
Common (≥1%)
hypoglycemia · weight gain · nausea · diarrhea · skin rashes
Rare but serious
severe hypoglycemia · hemolytic anemia (in G6PD deficiency) · agranulocytosis · thrombocytopenia · cholestatic hepatitis · hyponatremia · severe hypersensitivity reactions (e.g., Stevens-Johnson syndrome)
Pregnancy and lactation
FDA category: C
Pregnancy: Not recommended. Diabetes control should be managed with insulin during pregnancy. Lactation: Contraindicated.