Interactions : אינטראקציות

4.5 Interaction with other medicinal products and other forms of interaction

Glibenclamide is mainly metabolised by CYP 2C9 and to a lesser extent by CYP 3A4. This should be taken into account when glibenclamide is coadministered with inducers or inhibitors of CYP 2C9. Rifampicin may worsen glucose control of glibenclamide because rifampicin can significantly induce metabolic isozymes of glibenclamide such as CYP2C9 and 3A4.

Potentiation of the blood-glucose-lowering effect and, thus, in some instances hypoglycaemia may occur when taking other drugs, including: nonsteroidal anti- inflammatory agents, Insulin and other, oral antidiabetics, ACE inhibitors, disopyramide, fluoxetine, clarithromycin, and other drugs that are highly protein bound, anabolic steroids and male sex hormones, chloramphenicol, coumarin derivatives, cyclophosphamide, fenfluramine, fenyramidol, fibrates, ifosfamide, MAO inhibitors, miconazole, para-aminosalicyclic acid, pentoxifylline, phenylbutazone, azapropazone, oxyphenbutazone, probenecid, quinolones, salicylates, sulfinpyrazone, sulfonamides, sympatholytic agents such as beta- blockers and guanethidine, tetracyclines, tritoqualine, trosfosfamide. When such drugs are administered to a patient receiving GLUBEN, the patient should be observed closely for hypoglycemia. When such drugs are withdrawn from a patient receiving GLUBEN, the patient should be observed closely for loss of control.

Weakening of the blood-glucose-lowering effect and, thus, raised blood glucose levels may occur when taking other drugs, including: acetazolamide, barbiturates, corticosteroids, diazoxide, thiazides and other diuretics, epinephrine and other sympathomimetic agents, glucagon, laxatives, nicotinic acid, oestrogens and progestogens (oral contraceptives), calcium channel blocking drugs, isoniazid, phenothiazines, phenytoin, thyroid hormones, rifampicin. When such drugs are administered to a patient receiving GLUBEN, the patient should be closely observed for loss of control. When such drugs are withdrawn from a patient receiving GLUBEN, the patient should be observed closely for hypoglycemia.

H2-receptor antagonists, clonidine, and reserpine may lead to either potentiation or weakening of the blood-glucose-lowering effect.

Under the influence of sympatholytic drugs such as beta-blockers, clonidine, guanethidine, and resperine, the signs of adrenergic counter-regulation to hypoglycaemia may be reduced or absent.

Glibenclamide may increase cyclosporine plasma concentration and potentially lead to its increased toxicity. Monitoring and dosage adjustment of cyclosporine are therefore recommended when both drugs are coadministered.

Colesevelam binds glibenclamide and reduces glibenclamide absorption from the gastro-intestinal tract. No interaction was observed when glibenclamide was taken at least 4 hours before colesevelam. Therefore glibenclamide should be administered at least 4 hours prior to colesevelam.

A potential interaction between oral miconazole and oral hypoglycemic agents leading to severe hypoglycemia has been reported. Whether this interaction also occurs with the intravenous, topical or vaginal preparations of miconazole is not known.

A possible interaction between glybenclamide and fluoroquinolone antibiotics has been reported resulting in a potentiation of the hypoglycemic action of glibenclamide. The mechanism for this interaction is not known.

Both acute and chronic alcohol intake may potentiate or weaken the blood glucose lowering action of glibenclamide in an unpredicted fashion.

Glibenclamide may either potentiate or weaken the effect of coumarin derivatives. The mechanism of these interactions is not known.

Bosentan: An increased incidence of elevated liver enzymes was observed in patients receiving glibenclamide concomitantly with bosentan. Both glibenclamide and bosentan inhibit the bile salt export pump, leading to intracellular accumulation of cytotoxic bile salts. Therefore this combination should not be used.