Patients who take or discontinue taking certain other medicines while undergoing treatment with Amaryl may experience changes in blood sugar control. Based on experience with Amaryl and on what is known of other sulfonylureas, the following interactions must be considered: Glimepiride is metabolized by cytochrome P450 2C9 (CYP2C9). This should be taken into account when glimepiride is coadministered with inducers (e.g. rifampicin) or inhibitors (e.g. fluconazole) of CYP 2C9.
Potentiation of the blood-sugar-lowering effect and, thus, in some instances hypoglycaemia may occur when one of the following medicines is taken, for example: insulin and other oral anti-diabetics, ACE inhibitors, allopurinol, anabolic steroids and male sex hormones, chloramphenicol, coumarin derivatives, cyclophosphamide, disopyramide, fenfluramine, fenyramidol, fibrates, fluoxetine, guanethidine, ifosfamide, MAO inhibitors, miconazole, fluconazole, para-aminosalicylic acid, pentoxifylline (high dose parenteral), phenylbutazone, azapropazone, oxyphenbutazone, probenecid, quinolones, salicylates, sulfinpyrazone, clarithromycin, sulfonamides, tetracyclines, tritoqualine, trofosfamide.
Weakening of the blood-sugar-lowering effect and, thus, raised blood sugar levels may occur when one of the following medicines is taken, for example: acetazolamide, barbiturates, corticosteroids, diazoxide, diuretics, epinephrine (adrenaline) and other sympathomimetic agents, glucagons, laxatives (after protacted use), nicotinic acid (in high doses), oestrogens and progestogens, phenothiazines, phenytoin, rifampicin, thyroid hormones.
H2 receptor antagonists, clonidine and reserpine may lead to either potentiation or weakening of the blood-sugar-lowering effect. Beta-blockers decrease glucose tolerance. In patients with diabetes mellitus, this may lead to deterioration of metabolic control. In addition, beta-blockers may increase the tendency to hypoglycaemia (due to impaired counter-regulation). Under the influence of sympatholytic medicine such as beta-blockers, clonidine, guanethidine and reserpine, the signs of adrenergic counter-regulation to hypoglycaemia may be reduced or absent.
Both acute and chronic alcohol intake may potentiate or weaken the blood-sugar-lowering action of Amaryl unpredictably.
The effect of coumarin derivatives may be potentiated or weakened.
Bile acid sequestrant: Colesevelam binds to glimepiride and reduces glimepiride absorption from the gastrointestinal tract. No interaction was observed when glimepiride was taken at least 4 hours before colesevelam. Therefore glimepiride should be administered at least 4 hours prior to colesevelam.