Glyburide is an oral medicine used to treat type 2 diabetes, to lower blood sugar. It is taken with meals. The most important side effect is hypoglycaemia.
Also known as: Daonil
Voriconazole potentiates the effect of Glyburide (Glibenclamide), with a risk of hypoglycaemia.
Glyburide is metabolised by CYP2C9 (and CYP3A4), and voriconazole inhibits CYP2C9 and CYP3A4: the combination raises the sulfonylurea concentrations and the risk of hypoglycaemia — a mechanism analogous to that documented with fluconazole (glyburide AUC +44% and 5 of 20 volunteers requiring oral glucose in the fluconazole label study). Voriconazole also prolongs the QT and can cause hepatotoxicity. Monitor glycaemia closely at the start of the combination and whenever the antifungal dose changes, warn the patient about hypoglycaemia signs (sweating, tremor, palpitations, confusion) and consider reducing the glyburide dose.
Glyburide + voriconazole: voriconazole inhibits CYP2C9 and raises glyburide levels. Monitor glycaemia and adjust the sulfonylurea dose.
CYP2C9 inhibition by voriconazole reduces glibenclamide metabolism.
Capillary glucose, hypoglycaemia symptoms.
Severe hypoglycaemia.
Monitor blood glucose; a sulfonylurea dose reduction may be needed.
DailyMed/FDA (NIH/NLM) — approved Voriconazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f6a1a792-141b-42e8-8bd1-884e4408eb8a ; approved Glyburide (Glibenclamide) label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=524eec41-37ee-419a-b7a1-d23e888ae6ab — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Hypoglycaemia. Combining two oral antidiabetics requires dose adjustment and surveillance; not contraindicated.
Glibenclamide (sulphonylurea) stimulates insulin secretion and metformin reduces hepatic glucose production and improves insulin sensitivity — complementary and synergistic mechanisms, making the combination a usual option in type 2 diabetes. The main risk is hypoglycaemia, potentiated by the sulphonylurea, especially in the elderly, prolonged fasting, renal impairment or reduced food intake. Start with low doses, titrate slowly, educate the patient about hypoglycaemia signs and adjust glibenclamide with any deterioration of renal function.
Hypoglycaemia. Combining two oral antidiabetics requires dose adjustment and surveillance; not contraindicated.
Additive glucose-lowering effect: the sulfonylurea stimulates insulin and metformin reduces hepatic glucose output.
Capillary glucose and hypoglycaemia signs.
Tremor, sweating, confusion, pallor — signs of hypoglycaemia.
Start the sulfonylurea at a low dose and titrate on glucose readings.
DailyMed/FDA (NIH/NLM) — approved Glibenclamide label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=524eec41-37ee-419a-b7a1-d23e888ae6ab ; approved Metformin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=13b1e35f-d047-8ddc-e063-6394a90a24dd
Ciprofloxacin can cause severe hypoglycaemia in patients taking glyburide. Monitor blood glucose carefully during the antibiotic.
Case reports document severe, prolonged (correction-refractory) hypoglycaemia in diabetic patients on glyburide who started ciprofloxacin, including elevated serum glyburide levels. Fluoroquinolones interfere with insulin secretion; with sulfonylureas, the dysglycaemia risk is well documented. Close blood glucose monitoring is recommended during and after the antibiotic, especially in the elderly and in patients with renal impairment.
Documented cases of refractory hypoglycaemia with glyburide + ciprofloxacin. Monitor blood glucose during the antibiotic and treat any hypoglycaemia promptly.
Altered insulin secretion by fluoroquinolones, with additive risk with sulfonylureas.
Capillary glucose during the antibiotic.
Severe or prolonged hypoglycaemia — sweating, confusion, coma.
Reinforce self-monitoring of blood glucose; treat any hypoglycaemia immediately and reassess the sulfonylurea dose.
PubMed — https://pubmed.ncbi.nlm.nih.gov/10918110/ and https://pubmed.ncbi.nlm.nih.gov/15362597/ ; DailyMed/FDA (NIH/NLM) — approved Glyburide label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=524eec41-37ee-419a-b7a1-d23e888ae6ab ; approved Ciprofloxacin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=14c3bc33-201d-492e-9aee-a4d84c813a3d ; Prontuário Terapêutico do INFARMED (11th ed., 2012)
High-dose aspirin can increase the effect of glyburide and lower blood sugar too much. Monitor blood glucose.
The glimepiride SmPC (EMC-UK) and the glyburide label list salicylates among the drugs that potentiate the hypoglycaemic effect of sulfonylureas, through displacement from protein binding and an intrinsic hypoglycaemic effect at high doses. Antiplatelet-dose aspirin (75–100 mg) has a limited impact, but analgesic/anti-inflammatory doses require blood glucose monitoring.
High-dose salicylates potentiate the hypoglycaemic effect of sulfonylureas (protein displacement and an intrinsic hypoglycaemic effect). Monitor blood glucose; low-dose antiplatelet aspirin has a minimal effect.
Displacement from protein binding and an intrinsic hypoglycaemic effect of salicylates at high doses.
Capillary glucose; hypoglycaemia symptoms.
Hypoglycaemia — sweating, tremor, confusion.
Monitor blood glucose if high aspirin doses are used; prefer a low antiplatelet dose when possible.
DailyMed/FDA (NIH/NLM) — approved Glyburide label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=524eec41-37ee-419a-b7a1-d23e888ae6ab ; approved Aspirin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3ba0a9f2-062a-401e-82eb-54383a822366 ; EMC-UK (MHRA) — approved Glimepiride SmPC: https://www.medicines.org.uk/emc/product/10742/smpc ; Prontuário Terapêutico do INFARMED (11th ed., 2012)
Ibuprofen can increase the effect of glyburide and lower blood sugar too much. Monitor blood glucose if you take both.
The glimepiride SmPC (EMC-UK) includes non-steroidal anti-inflammatory drugs among the drugs that potentiate the hypoglycaemic effect of sulfonylureas. The mechanism involves displacement from protein binding and inhibition of metabolism. In diabetic patients, NSAID use should be accompanied by blood glucose monitoring, especially in prolonged courses.
NSAIDs potentiate the hypoglycaemic effect of sulfonylureas. Monitor blood glucose during ibuprofen use, especially at high doses or with prolonged use.
Displacement from protein binding and inhibition of sulfonylurea metabolism by NSAIDs.
Capillary glucose; hypoglycaemia symptoms.
Hypoglycaemia — sweating, tremor, confusion.
Monitor blood glucose during NSAID use; use the lowest dose and shortest duration possible.
EMC-UK (MHRA) — approved Glimepiride SmPC: https://www.medicines.org.uk/emc/product/10742/smpc ; DailyMed/FDA (NIH/NLM) — approved Glyburide label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=524eec41-37ee-419a-b7a1-d23e888ae6ab ; approved Ibuprofen label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=14515409-736f-4119-b6a0-cb19ee2e948e ; Prontuário Terapêutico do INFARMED (11th ed., 2012)
Co-trimoxazole can enhance the effect of glyburide and lower blood sugar too much. Monitor blood glucose during the antibiotic.
Sulfamethoxazole (a component of co-trimoxazole) is a sulphonamide that potentiates the hypoglycaemic effect of sulfonylureas through protein displacement and inhibition of metabolism — a classic, well-documented interaction (the glimepiride SmPC lists sulphonamides among the drugs that potentiate hypoglycaemia). This combination is common (urinary infections in diabetics) and requires blood glucose monitoring.
Sulphonamides (sulfamethoxazole) potentiate sulfonylurea hypoglycaemia. Monitor blood glucose during the antibiotic; consider a sulfonylurea dose reduction.
Protein displacement and inhibition of sulfonylurea metabolism by the sulphonamide.
Capillary glucose; hypoglycaemia symptoms.
Severe hypoglycaemia — sweating, confusion, coma.
Monitor blood glucose during the antibiotic; consider a temporary sulfonylurea dose reduction.
EMC-UK (MHRA) — approved Glimepiride SmPC: https://www.medicines.org.uk/emc/product/10742/smpc ; DailyMed/FDA (NIH/NLM) — approved Glyburide label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=524eec41-37ee-419a-b7a1-d23e888ae6ab ; approved Co-trimoxazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=08500fcb-dbec-4ac2-91c3-189d27907ec0 ; Prontuário Terapêutico do INFARMED (11th ed., 2012)
Fluconazole potentiates the effect of Glyburide (Glibenclamide), with a risk of severe hypoglycaemia.
Fluconazole inhibits CYP2C9 and CYP3A4, the enzymes that metabolise glyburide (a sulfonylurea); in the pharmacokinetic study of the fluconazole label with 20 volunteers, glyburide (5 mg single dose) AUC and Cmax increased significantly after fluconazole administration — AUC +44% ± 29% and Cmax +19% ± 19% — and 5 of the 20 volunteers required oral glucose after glyburide ingestion at 7 days of fluconazole. Across the three sulfonylurea studies (tolbutamide, glipizide, glyburide), 47.8% of fluconazole-treated patients experienced symptoms consistent with hypoglycaemia. The label recommends carefully monitoring blood glucose and adjusting the sulfonylurea dose as necessary. In practice, warn the patient about hypoglycaemia signs (sweating, tremor, palpitations, confusion) and consider reducing the glyburide dose or preferring a sulfonylurea less dependent on CYP2C9 for the duration of the antifungal.
Fluconazole + glyburide: fluconazole inhibits CYP2C9 and raises glyburide levels (AUC +44%), with a risk of hypoglycaemia. Monitor glycaemia and adjust the sulfonylurea dose.
CYP2C9 inhibition by fluconazole reduces glibenclamide metabolism, increasing its concentrations.
Capillary glucose, hypoglycaemia symptoms (tremor, sweating, confusion).
Severe hypoglycaemia (loss of consciousness, seizures).
Monitor blood glucose more frequently; a sulfonylurea dose reduction may be needed.
DailyMed/FDA (NIH/NLM) — approved Fluconazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7961c029-746c-48c3-888b-8f8344102873 ; approved Glyburide (Glibenclamide) label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=524eec41-37ee-419a-b7a1-d23e888ae6ab — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Hypoglycaemia is more likely when alcohol is ingested (especially with fasting or strenuous exercise); alcohol can also mask the warning signs.
Avoid alcohol, especially on an empty stomach; monitor blood glucose after intake.
DailyMed/FDA (NIH/NLM) — approved Glyburide label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=524eec41-37ee-419a-b7a1-d23e888ae6ab
Renal impairment raises glyburide levels and increases the risk of severe hypoglycaemia; hypoglycaemia may be difficult to recognise.
Use with caution in renal impairment, starting at a low dose and monitoring blood glucose; consider insulin in significant renal impairment.
DailyMed/FDA (NIH/NLM) — approved Glyburide label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=524eec41-37ee-419a-b7a1-d23e888ae6ab
Hepatic impairment raises glyburide levels and reduces gluconeogenic capacity, increasing the risk of severe hypoglycaemia.
Use with caution in hepatic impairment; monitor blood glucose and consider insulin in significant liver disease.
DailyMed/FDA (NIH/NLM) — approved Glyburide label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=524eec41-37ee-419a-b7a1-d23e888ae6ab
Treatment of patients with G6PD deficiency with sulfonylureas can lead to haemolytic anaemia.
Consider a non-sulfonylurea alternative in patients with G6PD deficiency; watch for signs of haemolysis.
DailyMed/FDA (NIH/NLM) — approved Glyburide label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=524eec41-37ee-419a-b7a1-d23e888ae6ab
Sulfonylureas cross the placenta; insulin is the first-line drug in pregnancy, but glyburide has been used in some protocols with monitoring.
Prefer insulin; if glyburide is kept (selected protocols), monitor maternal glucose and fetal growth.
There is a risk of hypoglycaemia in the infant; use with caution during breastfeeding and monitor the infant.
No specific data; pregnancy planning with transition to insulin as guided.
DailyMed/FDA (NIH/NLM) — approved Glyburide label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=524eec41-37ee-419a-b7a1-d23e888ae6ab
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Sulfonylurea that acutely lowers blood glucose by stimulating the release of insulin from the pancreas, an effect dependent on functioning beta cells. The blood glucose lowering effect persists for 24 hours following a single morning dose in diabetic patients. It also produces a mild diuresis by enhancing renal free water clearance.
Stimulates the release of insulin from pancreatic beta cells (dependent on functioning beta cells); extrapancreatic effects may be involved. The combination with metformin is synergistic through different but complementary mechanisms.
Significant absorption within one hour of dosing, peak plasma concentrations at about 4 hours and low but detectable levels at 24 hours. Sulfonylureas are extensively bound to serum proteins; glyburide binding is predominantly non-ionic.
The major metabolite is the 4-trans-hydroxy derivative, with a second, the 3-cis-hydroxy derivative; both have weak hypoglycaemic activity. Glyburide is excreted as metabolites in bile and urine, approximately 50% by each route — a pattern different from other sulfonylureas, which are eliminated mainly in urine.
The decline of glyburide in serum is biphasic, with a terminal half-life of about 10 hours.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
