Sulfonylurea (oral antidiabetic)
Gliclazide is an oral medicine used to treat type 2 diabetes, to lower blood sugar. It is taken with breakfast. The most important side effect is hypoglycaemia.
Also known as: Diamicron
Fluconazole can increase the effect of gliclazide and lower blood sugar too much. Monitor blood glucose during the antifungal.
The gliclazide SmPC (EMC-UK) lists fluconazole among the drugs that potentiate the hypoglycaemic effect of sulfonylureas, with possible symptomatic hypoglycaemia or coma. The mechanism involves inhibition of CYP2C9 (gliclazide metabolism) and excretion. Blood glucose monitoring is mandatory during the combination.
Fluconazole potentiates the hypoglycaemic effect of gliclazide (CYP2C9 inhibition and reduced elimination). Caution with blood glucose monitoring; a dose adjustment may be needed.
CYP2C9 inhibition and reduced gliclazide elimination by fluconazole.
Capillary glucose; hypoglycaemia symptoms.
Severe hypoglycaemia — sweating, confusion, coma.
Prefer an alternative antifungal when possible; otherwise, monitor blood glucose and consider a sulfonylurea dose reduction.
EMC-UK (MHRA) — approved Gliclazide SmPC: https://www.medicines.org.uk/emc/product/1321/smpc ; DailyMed/FDA (NIH/NLM) — approved Fluconazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7961c029-746c-48c3-888b-8f8344102873 ; Prontuário Terapêutico do INFARMED (11th ed., 2012)
Ciprofloxacin can alter blood sugar in patients taking gliclazide, especially the elderly. Monitor blood glucose during the antibiotic.
The gliclazide SmPC (EMC-UK) explicitly mentions blood glucose disturbances, including hypo- and hyperglycaemia, in diabetic patients treated with fluoroquinolones, especially the elderly, recommending careful blood glucose monitoring in all patients on the combination. The mechanism involves fluoroquinolone-induced changes in insulin secretion.
The gliclazide SmPC (EMC-UK) recommends careful blood glucose monitoring with fluoroquinolones (dysglycaemia, especially in the elderly). Watch for hypo- and hyperglycaemia during and after the antibiotic.
Fluoroquinolone-induced changes in insulin secretion.
Capillary glucose; symptoms of hypo/hyperglycaemia.
Confusion, sweating, polyuria, intense thirst, coma — medical attention.
Monitor blood glucose daily during the antibiotic; instruct the patient on the signs of dysglycaemia.
EMC-UK (MHRA) — approved Gliclazide SmPC: https://www.medicines.org.uk/emc/product/1321/smpc ; DailyMed/FDA (NIH/NLM) — approved Ciprofloxacin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=14c3bc33-201d-492e-9aee-a4d84c813a3d ; Prontuário Terapêutico do INFARMED (11th ed., 2012)
Gliclazide can increase the effect of warfarin and the risk of bleeding. The INR should be checked more often.
The gliclazide SmPC (EMC-UK) states that sulfonylureas may potentiate anticoagulation during concurrent treatment with coumarins (e.g. warfarin), and the anticoagulant dose may need adjustment. The mechanism involves displacement from protein binding and inhibition of coumarin metabolism. The combination is common (type 2 diabetes and atrial fibrillation).
Sulfonylureas may potentiate anticoagulation during concurrent treatment; the anticoagulant dose may need adjustment. Monitor INR.
Displacement from protein binding and inhibition of coumarin metabolism.
Periodic INR and bleeding symptoms.
Melena, haematemesis, bruising — seek immediate care.
Monitor INR when starting, adjusting or stopping gliclazide and adjust the anticoagulant dose.
EMC-UK (MHRA) — approved Gliclazide SmPC: https://www.medicines.org.uk/emc/product/1321/smpc ; DailyMed/FDA (NIH/NLM) — approved Warfarin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=541c9a70-adaf-4ef3-94ba-ad4e70dfa057 ; Prontuário Terapêutico do INFARMED (11th ed., 2012)
Combining gliclazide with pioglitazone increases the risk of hypoglycaemia. Your doctor may reduce the gliclazide dose.
Pioglitazone improves insulin sensitivity; with sulfonylureas, the effect on blood glucose is additive and the risk of hypoglycaemia increases, requiring a secretagogue dose reduction. The pioglitazone label (DailyMed) recommends a lower dose of insulin or secretagogues when combined. The combination is used in poorly controlled type 2 diabetes.
Thiazolidinedione + sulfonylurea: additive hypoglycaemic effect; a sulfonylurea dose reduction may be needed. Also watch for pioglitazone fluid retention/oedema.
Additive hypoglycaemic effect of insulin sensitisation with secretion stimulation.
Capillary glucose; oedema and signs of heart failure.
Hypoglycaemia; sudden oedema, dyspnoea.
Reduce the sulfonylurea dose when starting pioglitazone and monitor blood glucose in the first weeks.
DailyMed/FDA (NIH/NLM) — approved Pioglitazone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=31619517-a590-408a-ae9e-76c99f0a0a1d ; EMC-UK (MHRA) — approved Gliclazide SmPC: https://www.medicines.org.uk/emc/product/1321/smpc ; Prontuário Terapêutico do INFARMED (11th ed., 2012)
Alcohol increases the hypoglycaemic reaction (by inhibiting compensatory mechanisms) and can lead to hypoglycaemic coma.
Avoid alcohol and alcohol-containing medicines during treatment with gliclazide.
EMC-UK (MHRA) — approved Gliclazide SmPC: https://www.medicines.org.uk/emc/product/1321/smpc
Taking with breakfast reduces gastrointestinal disturbances, and regular carbohydrate intake is important (delayed meals increase hypoglycaemia).
Take with breakfast and keep regular meals with an adequate carbohydrate intake.
EMC-UK (MHRA) — approved Gliclazide SmPC: https://www.medicines.org.uk/emc/product/1321/smpc
Severe renal impairment is a contraindication to gliclazide (insulin is recommended); hypoglycaemia in these patients can be prolonged.
Do not use gliclazide in severe renal impairment; switch to insulin.
EMC-UK (MHRA) — approved Gliclazide SmPC: https://www.medicines.org.uk/emc/product/1321/smpc
Severe hepatic impairment is a contraindication to gliclazide (insulin is recommended); the risk of prolonged hypoglycaemia is increased.
Do not use gliclazide in severe hepatic impairment; switch to insulin.
EMC-UK (MHRA) — approved Gliclazide SmPC: https://www.medicines.org.uk/emc/product/1321/smpc
Oral antidiabetics are not suitable in pregnancy; insulin is the first-choice drug and gliclazide should be replaced before conception or as soon as pregnancy is detected.
Do not use in any trimester; switch to insulin before a planned pregnancy or as soon as pregnancy is discovered.
Excretion into milk is unknown; contraindicated during breastfeeding due to the risk of neonatal hypoglycaemia.
No specific data; pregnancy planning with transition to insulin.
EMC-UK (MHRA) — approved Gliclazide SmPC: https://www.medicines.org.uk/emc/product/1321/smpc
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Second-generation sulfonylurea indicated in type 2 diabetes when diet, exercise and weight loss are insufficient. It restores the early peak of glucose-stimulated insulin secretion and reduces postprandial hyperglycaemia; it reduces glycated haemoglobin (HbA1c) and blood glucose.
Sulfonylurea: binds to the sulfonylurea receptor on pancreatic beta-cell membranes, closing the ATP-sensitive potassium channel; the resulting depolarisation opens voltage-dependent calcium channels and stimulates insulin release. It also has antioxidant and haemovascular properties described in the SmPC.
Well absorbed after oral administration; peak plasma concentrations are reached between 2 and 6 hours after dosing. Plasma protein binding is about 94%.
Extensively metabolised in the liver (hydroxylation and oxidation), with formation of metabolites without relevant hypoglycaemic activity. The metabolites are eliminated in urine (60 to 70%) and faeces (10 to 20%).
The elimination half-life is of the order of 10 to 20 hours, allowing daily dosing; the half-life may be prolonged in the elderly and with high doses.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
