Sulfonylurea (oral antidiabetic)
Glimepiride is an oral medicine used to treat type 2 diabetes, to lower blood sugar. It is taken once a day with the first meal. The most important side effect is hypoglycaemia (blood sugar too low).
Also known as: Amaryl
DailyMed/FDA (NIH/NLM) — approved Glimepiride label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fc9d8495-184c-3af1-e053-6394a90a5e29 ; EMC-UK (MHRA) — approved Glimepiride SmPC: https://www.medicines.org.uk/emc/product/10742/smpc — with additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Taking fluconazole with glimepiride can lower blood sugar too much (hypoglycaemia). Watch for the signs and tell your doctor.
Glimepiride is metabolised by CYP2C9; fluconazole is one of the most potent inhibitors of this isoenzyme. An in vivo study cited in the SmPC (EMC-UK) shows an approximately 2-fold increase in glimepiride AUC with fluconazole. The resulting hypoglycaemia can be severe and prolonged, especially in the elderly and in patients with impaired renal function. This is a common combination in community pharmacy (vaginal/oral candidiasis in diabetic patients).
Fluconazole (a potent CYP2C9 inhibitor) increases glimepiride AUC by about 2-fold, with a risk of severe hypoglycaemia. If the combination is unavoidable, monitor blood glucose and consider reducing the sulfonylurea dose.
CYP2C9 inhibition by fluconazole, reducing glimepiride metabolism.
Capillary glucose; hypoglycaemia symptoms.
Sweating, tremor, confusion, intense hunger, loss of consciousness — treat hypoglycaemia immediately.
Avoid when possible; if needed, reduce the glimepiride dose and reinforce self-monitoring of blood glucose during and after antifungal treatment.
EMC-UK (MHRA) — approved Glimepiride SmPC: https://www.medicines.org.uk/emc/product/10742/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 lower blood sugar too much in patients taking glimepiride. Monitor blood glucose carefully during the antibiotic.
Fluoroquinolones, including ciprofloxacin, alter glycaemic control through mechanisms that are not fully understood (blockade of ATP-dependent potassium channels in beta cells and altered insulin secretion). Documented cases of refractory hypoglycaemia with glyburide and ciprofloxacin exist, and the gliclazide SmPC (EMC-UK) recommends careful blood glucose monitoring in all patients on sulfonylureas and fluoroquinolones, with special attention to the elderly.
Fluoroquinolones can cause dysglycaemia (hypo- or hyperglycaemia) in diabetic patients, especially the elderly; with sulfonylureas there is a documented risk of severe, prolonged hypoglycaemia. Monitor blood glucose during the antibiotic.
Altered insulin secretion by fluoroquinolones, with additive risk with sulfonylureas.
Daily capillary glucose during the antibiotic.
Severe or prolonged hypoglycaemia; confusion, sweating, coma — seek immediate medical care.
Reinforce self-monitoring of blood glucose during the antibiotic; educate the patient on the signs of hypo- and hyperglycaemia.
PubMed — https://pubmed.ncbi.nlm.nih.gov/10918110/ and https://pubmed.ncbi.nlm.nih.gov/15362597/ ; EMC-UK (MHRA) — approved Glimepiride SmPC: https://www.medicines.org.uk/emc/product/10742/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)
Co-trimoxazole can enhance the effect of glimepiride and lower blood sugar too much. Monitor blood glucose during treatment.
Sulphonamides potentiate the hypoglycaemic effect of sulfonylureas through multiple mechanisms: displacement from plasma protein binding, inhibition of metabolism and reduced renal excretion. The glimepiride SmPC (EMC-UK) lists long-acting sulphonamides among the drugs that potentiate the hypoglycaemic effect. This combination is common (urinary and respiratory infections in diabetics).
Sulphonamides (sulfamethoxazole in co-trimoxazole) potentiate sulfonylurea hypoglycaemia through protein displacement and reduced elimination. Monitor blood glucose and consider a dose reduction.
Protein displacement and inhibition of glimepiride metabolism by sulphonamides.
Capillary glucose; hypoglycaemia symptoms.
Severe hypoglycaemia — sweating, tremor, confusion, loss of consciousness.
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 Co-trimoxazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=08500fcb-dbec-4ac2-91c3-189d27907ec0 ; Prontuário Terapêutico do INFARMED (11th ed., 2012)
Fluoxetine can increase the effect of glimepiride and lower blood sugar too much. Watch for the signs of hypoglycaemia.
The glimepiride SmPC (EMC-UK) lists fluoxetine and MAOIs among the drugs that may potentiate the hypoglycaemic effect of sulfonylureas, through mechanisms involving enzyme inhibition and altered insulin sensitivity. Blood glucose monitoring is recommended at the start and during SSRI treatment, particularly in the first days.
The glimepiride SmPC (EMC-UK) lists fluoxetine among the drugs that potentiate the hypoglycaemic effect. Monitor blood glucose when starting or adjusting the SSRI.
Enzyme inhibition and altered insulin sensitivity by fluoxetine.
Capillary glucose at the start of SSRI treatment.
Hypoglycaemia — tremor, sweating, confusion.
Reinforce self-monitoring of blood glucose when starting fluoxetine; adjust the sulfonylurea dose if needed.
EMC-UK (MHRA) — approved Glimepiride SmPC: https://www.medicines.org.uk/emc/product/10742/smpc ; DailyMed/FDA (NIH/NLM) — approved Fluoxetine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=09fb3100-1e06-4cdc-8016-7e4f5d097490 ; Prontuário Terapêutico do INFARMED (11th ed., 2012)
Combining glimepiride with pioglitazone increases the risk of hypoglycaemia. If used together, your doctor may reduce the glimepiride dose.
Pioglitazone sensitises tissues to insulin; when combined with a sulfonylurea (secretagogue), the hypoglycaemic effect is additive. The approved pioglitazone label (DailyMed) states that, when used with insulin or secretagogues, a lower dose of these may be needed to reduce the risk of hypoglycaemia. This combination is common in type 2 diabetes combination therapy.
Combining a thiazolidinedione with an insulin secretagogue increases the risk of hypoglycaemia; the sulfonylurea dose may need to be reduced (and pioglitazone if oedema/heart failure).
Additive hypoglycaemic effect of insulin sensitisation with secretion stimulation.
Capillary glucose; signs of fluid retention/oedema (pioglitazone effect).
Hypoglycaemia; sudden oedema, shortness of breath (heart failure) — medical attention.
If the combination is needed, reduce the sulfonylurea dose and monitor blood glucose, especially 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 Glimepiride SmPC: https://www.medicines.org.uk/emc/product/10742/smpc ; Prontuário Terapêutico do INFARMED (11th ed., 2012)
Alcohol can potentiate or weaken the hypoglycaemic effect of glimepiride unpredictably; drinking with skipped meals increases the risk of severe hypoglycaemia.
Limit alcohol intake and never drink on an empty stomach; reinforce self-monitoring of blood glucose after drinking alcohol.
EMC-UK (MHRA) — approved Glimepiride SmPC: https://www.medicines.org.uk/emc/product/10742/smpc
Glimepiride should be taken immediately before or during the first main meal; irregular or skipped meals increase the risk of hypoglycaemia.
Take glimepiride with the first meal of the day, always at the same time, and keep regular meals.
EMC-UK (MHRA) — approved Glimepiride SmPC: https://www.medicines.org.uk/emc/product/10742/smpc ; DailyMed/FDA (NIH/NLM) — approved Glimepiride label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fc9d8495-184c-3af1-e053-6394a90a5e29
Renal impairment raises glimepiride levels and increases the risk of severe, prolonged hypoglycaemia.
Start at a low dose (1 mg) and titrate slowly; monitor blood glucose; in severe renal impairment, switch to insulin.
DailyMed/FDA (NIH/NLM) — approved Glimepiride label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fc9d8495-184c-3af1-e053-6394a90a5e29 ; EMC-UK (MHRA) — approved Glimepiride SmPC: https://www.medicines.org.uk/emc/product/10742/smpc
Severe hepatic impairment alters glimepiride pharmacokinetics and reduces gluconeogenic capacity, greatly increasing the risk of hypoglycaemia; switching to insulin is indicated.
Do not use glimepiride in severe hepatic impairment; switch to insulin.
EMC-UK (MHRA) — approved Glimepiride SmPC: https://www.medicines.org.uk/emc/product/10742/smpc
Sulfonylureas can cause haemolytic anaemia in patients with G6PD deficiency.
Consider a non-sulfonylurea alternative in patients with G6PD deficiency; watch for signs of haemolysis if the drug is kept.
DailyMed/FDA (NIH/NLM) — approved Glimepiride label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fc9d8495-184c-3af1-e053-6394a90a5e29
Glimepiride should not be used during pregnancy; insulin is the first-line drug for glycaemic control in pregnancy.
Do not use in any trimester; if pregnancy is planned or detected, switch to insulin as early as possible.
Like other sulfonylureas, it is excreted into milk and there is a risk of hypoglycaemia in the infant — breastfeeding is not recommended during treatment.
No specific data; contraception is recommended if pregnancy is not desired, with planned transition to insulin.
EMC-UK (MHRA) — approved Glimepiride SmPC: https://www.medicines.org.uk/emc/product/10742/smpc
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Sulfonylurea that lowers blood glucose primarily by stimulating insulin release from pancreatic beta cells. The maximum effect (minimum blood glucose) occurs about 2 to 3 hours after single oral doses. It improves HbA1c, fasting plasma glucose and postprandial glucose.
Binds to the sulfonylurea receptor in the pancreatic beta-cell plasma membrane, closing the ATP-sensitive potassium channel and stimulating insulin release.
Peak concentrations occur 2 to 3 hours after dosing. Bioavailability is essentially complete; food decreases Cmax and AUC by 8 and 9%. Protein binding is greater than 99.5% and the volume of distribution is 8.8 L.
Completely metabolised by oxidative biotransformation: CYP2C9 converts glimepiride to the M1 metabolite (about one third of the activity), which is then converted to the inactive M2. About 60% of the radioactivity is recovered in urine within 7 days and 40% in faeces; no parent drug is recovered.
After intravenous administration, the terminal half-life is about 5 hours after a single dose, prolonging to about 9 hours with multiple dosing; the half-life is unchanged in renal impairment.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
