Glyzeric Drug Interactions

Gliclazide: The following products are likely to increase the risk of hypoglycaemia.
Contraindicated combination: Miconazole (systemic route, oromucosal gel): increases the hypoglycaemic effect with possible onset of hypoglycaemic symptoms, or even coma.
Antibacterials: Sulfonamides may enhance the hypoglycaemic effect of gliclazide.
Combinations which are not recommended: Phenylbutazone (systemic route): increases the hypoglycaemic effect of sulfonylureas (displaces their binding to plasma proteins and/or reduces their elimination).
It is preferable to use a different anti-inflammatory agent, or else to warn the patient and emphasise the importance of self-monitoring. Where necessary, adjust the dose during and after treatment with the anti-inflammatory agent.
Alcohol: increases the hypoglycaemic reaction (by inhibiting compensatory reactions) that can lead to the onset of hypoglycaemic coma.
Avoid alcohol or medicines containing alcohol.
Combinations requiring precautions for use: Potentiation of the blood glucose lowering effect and thus, in some instances, hypoglycaemia may occur when one of the following drugs is taken: other antidiabetic agents (insulins, acarbose, metformin, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, GLP-1 receptor agonists), beta-blockers, fluconazole, angiotensin converting enzyme inhibitors (captopril, enalapril), H2-receptor antagonists, MAOIs, sulfonamides, clarithromycin and nonsteroidal anti-inflammatory agents.
Anti-gout agents: Enhanced hypoglycaemic effect with allopurinol, sulfinpyrazone and probenecid.
Chloramphenicol: Enhances the hypoglycaemic effect of sulfonylureas.
Beta-blockers: May reduce the hypoglycaemic effects of sulphonylureas, and mask the symptoms of hypoglycaemia.
Fluconazole: May enhance the hypoglycaemic effect of sulphonylureas.
ACE inhibitors: Such as captopril and enalapril, may enhance the hypoglycaemic effect of gliclazide.
Antimalarials: Possible increase in hypoglycaemia with quinine and quinidine.
Lipid-lowering drugs: Clofibrate group drugs may improve glucose tolerance and have an additive effect.
Sex hormones, hormone antagonists and steroids: Testosterone, and anabolic steroids may enhance the hypoglycaemic effect of gliclazide. Octreotide may cause hypoglycaemia.
The following products may cause an increase in blood glucose levels.
Combination which is not recommended: Danazol: diabetogenic effect of danazol.
If the use of this active substance cannot be avoided, warn the patient and emphasise the importance of urine and blood glucose monitoring. It may be necessary to adjust the dose of the antidiabetic agent during and after treatment with danazol.
Combinations requiring precautions during use: Chlorpromazine (neuroleptic agent): high doses (>100 mg per day of chlorpromazine) increase blood glucose levels (reduced insulin release).
Warn the patient and emphasise the importance of blood glucose monitoring. It may be necessary to adjust the dose of the antidiabetic active substance during and after treatment with the neuroleptic agent.
Glucocorticoids (systemic and local route: intra-articular, cutaneous and rectal preparations) and tetracosactrin: increase in blood glucose levels with possible ketosis (reduced tolerance to carbohydrates due to glucocorticoids).
Warn the patient and emphasise the importance of blood glucose monitoring, particularly at the start of treatment. It may be necessary to adjust the dose of the antidiabetic active substance during and after treatment with glucocorticoids.
Ritodrine, salbutamol, terbutaline: (I.V.): Increased blood glucose levels due to beta-2 agonist effects.
Emphasise the importance of monitoring blood glucose levels. If necessary, switch to insulin.
Saint John's Wort (Hypericum perforatum) preparations: Gliclazide exposure is decreased by Saint John's Wort-Hypericum perforatum.
Emphasize the importance of blood glucose levels monitoring.
Cytotoxic drugs: Crisantaspase may induce hyperglycaemia and the dose of gliclazide may need to be adjusted.
Antibacterials: Isoniazid may increase blood sugar levels, so the dose of sulphonylurea may need to be adjusted. Rifamycins may reduce the hypoglycaemic effect of sulphonylureas.
Antihypertensives: Diazoxide may reduce the hypoglycaemic effect of sulphonylureas.
Antipsychotics: Chlorpromazine in daily doses of 100mg or more can reduce the hypoglycaemic effect of sulphonylureas.
Diuretics: Loop and thiazide diuretics may reduce the hypoglycaemic effect of sulphonylureas.
Lithium: May occasionally impair glucose tolerance.
Sex hormones, hormone antagonists and steroids: Oestrogens, progesterones, oral contraceptives and corticosteroids may reduce the hypoglycaemic effect of sulphonylureas.
Octreotide may cause hyperglycaemia.
Thyroid hormones: May reduce the effect of sulphonylureas.
Combination which must be taken into account: Anticoagulant therapy (Warfarin): Sulfonylureas may lead to potentiation of anticoagulation during concurrent treatment.
Adjustment of the anticoagulant may be necessary.
Metformin: Concomitant use not recommended: Alcohol: Alcohol intoxication is associated with an increased risk of lactic acidosis, particularly in case of fasting, malnutrition or hepatic impairment.
Iodinated contrast agents: Metformin must be discontinued prior to or at the time of the imaging procedure and not restarted until at least 48 hours after, provided that renal function has been re-evaluated and found to be stable.
Combinations requiring precautions for use: Some medicinal products can adversely affect renal function which may increase the risk of lactic acidosis, e.g. NSAIDs, including selective cyclo-oxygenase (COX) II inhibitors, ACE inhibitors, angiotensin II receptor antagonists and diuretics, especially loop diuretics. When starting or using such products in combination with metformin, close monitoring of renal function is necessary.
Medicinal products with intrinsic hyperglycaemic activity (e.g. glucocorticoids (systemic and local routes) and sympathomimetics).
More frequent blood glucose monitoring may be required, especially at the beginning of treatment. If necessary, adjust the metformin dosage during therapy with the respective medicinal product and upon its discontinuation.
Organic cation transporters (OCT): Metformin is a substrate of both transporters OCT1 and OCT2.
Co-administration of metformin with: Inhibitors of OCT1 (such as verapamil) may reduce efficacy of metformin.
Inducers of OCT1 (such as rifampicin) may increase gastrointestinal absorption and efficacy of metformin.
Inhibitors of OCT2 (such as cimetidine, dolutegravir, ranolazine, trimethoprime, vandetanib, isavuconazole) may decrease the renal elimination of metformin and thus lead to an increase in metformin plasma concentration.
Inhibitors of both OCT1 and OCT2 (such as crizotinib, olaparib) may alter efficacy and renal elimination of metformin.
Caution is therefore advised, especially in patients with renal impairment, when these drugs are co-administered with metformin, as metformin plasma concentration may increase. If needed, dose adjustment of metformin may be considered as OCT inhibitors/Inducers may alter the efficacy of metformin.