Amaryl M Drug Interactions

Glimepiride: When other drugs are concomitantly administered to or withdrawn from a patient receiving this drug, both undesired increases and decreases in the hypoglycemic action of glimepiride can occur.
Based on experience with glimepiride and other sulfonylureas, the following interactions must be considered: Glimepiride is metabolized by cytochrome P450 2C9 (CYP2C9). Its metabolism is known to be influenced by concomitant administration of CYP2C9 inducers (e.g., rifampicin) or inhibitors (e.g., fluconazole).
Potentiation of the blood-glucose-lowering effect and, thus, in some instances hypoglycaemia may occur when one of the following drugs is taken, for example: insulin and other oral antidiabetics; 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; sulfonamide antibiotics; tetracyclines; tritoqualine; trofosfamide.
Weakening of the blood-glucose-lowering effect and, thus raised blood glucose levels may occur when one of the following drugs is taken, for example: acetazolamide; barbiturates; corticosteroids; diazoxide; diuretics; epinephrine (adrenaline) and other sympathomimetic agents; glucagon; laxatives (long term 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-glucose-lowering effect.
Beta-blockers reduce glucose tolerance. Reduction of glucose tolerance may change metabolic control. Beta-blockers may increase the risk of hypoglycemia (due to failure of counter-regulation).
Under the influence of sympatholytic drugs 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-glucose-lowering action of glimepiride in an unpredictable fashion.
The effect of coumarin derivatives may be potentiated or weakened.
Bile acid sequestrant: Colesevelam binds to glimepiride and reduces glimepiride absorption from the gastro-intestinal 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.
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 insufficiency. Avoid consumption of alcohol and alcohol-containing medications.
Iodinated contrast agents: Metformin should be discontinued at the time of or prior to the procedure, and withheld for 48hours subsequent to the procedure and reinstituted only after renal function has been re-evaluated and found to be normal. (See Contraindications and Warnings).
Combinations requiring precautions for use: Medicinal products with intrinsic hyperglicaemic activity (e.g. glucocorticoids and tetracosactides (systemic and local routes), beta-2-agonists, danazol, and chlorpromazine at high dosages of 100 mg per day, diuretics): 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.
Diuretics, especially loop diuretics, may increase the risk of lactic acidosis due to their potential to decrease renal function (further to their intrinsic hyperglycaemic effect, see previous text).
ACE-inhibitors may decrease the blood glucose levels. If necessary, adjust the dosage of the antidiabetic drug during therapy with the other drug and upon its discontinuation.
Others: Lactic acidosis may occur by concomitant administration with antibiotics having strong nephrotoxicity (gentamicin, etc).
The hypoglycemic action of co-administration with the following drugs may be potentiated or weakened. When these drugs are administered, the blood glucose level and patient should be observed closely.
Drugs potentiating the effect Insulin, sulfonamides, and sulfonylureas products, Anabolic steroids, guanethidine, salicylates (aspirin, etc), beta-blockers(propranolol, etc), MAO inhibitors.
Drugs weakening the effect. Epinephrine, corticosteroids, thyroid hormones, estrogens, diuretics, pyrazinamide, isoniazid, nicotinic acid, phenothiazines.
Glyburide: In a single-dose interaction study in type 2 diabetes subjects, co-administration of metformin and glyburide did not result on any changes in either metformin pharmacokinetics or pharmacodynamics. Decreases in glyburide AUC and Cmax were observed, but were highly variable. The single-dose nature of this study and the lack of correlation between glyburide blood levels and pharmacodynamics effects, makes the clinical significance of this interaction uncertain.
Furosemide: A single-dose, metformin-furosemide drug interaction study in healthy subjects demonstrated that pharmacokinetic parameters of both compounds were affected by co-administration. Furosemide increased the metformin plasma and blood Cmax by 22% and blood AUC by 15%, without any significant change in metformin renal clearance. When administered with metformin, the Cmax and AUC of furosemide were 31% and 12% smaller, respectively, than when administered alone, and the terminal half-life was decreased by 32%, without any significant change in furosemide renal clearance. No information is available about the interaction of metformin and furosemide when co-administered chronically.
Nifedipine: A single-dose, metformin-nifedipine drug interaction study in normal healthy volunteers demonstrated that co-administration of nifedipine increased plasma metformin Cmax and AUC by 20% and 9%, respectively, and increased the amount excreted in the urine. Metformin had minimal effects on nifedipine.
Cationic drugs: Cationic drugs (e.g. amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, and vancomycin) that are eliminated by renal tubular secretion theoretically have the potential for interaction with metformin by competing for common renal tubular transport systems. Such interaction between metformin and oral cimetidine has been observed in normal healthy volunteers in both single- and multiple- dose, metformin-cimetidine drug interaction studies, with a 60% increase in peak metformin plasma and whole blood concentrations and a 40% increase in plasma and whole blood metformin AUC. There was no change in elimination half-life in the single-dose study. Metformin had no effect on cimetidine pharmacokinetics. Although such interactions remain theoretical (except for cimetidine), careful patient monitoring and dose adjustment of metformin and/or the interfering drug is recommended in patients who are taking cationic medications that are excreted via the proximal renal tubular secretory system.
Other: Certain drugs tend to produce hyperglycemia and may lead to loss of glycemic control. These drugs include thiazide and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, and isoniazid. When such drugs are administered to a patient receiving metformin, the patient should be closely observed to maintain adequate glycemic control.
In healthy volunteers, the pharmacokinetics of metformin and propranolol and metformin and ibuprofen were not affected when co-administered in single-dose interaction studies. Metformin is negligibly bound to plasma proteins and is, therefore, less likely to interact with highly protein-bound drugs such as salicylates, sulfonamides, chloramphenicol, and probenecid, as compared to the sulfonylureas, which are extensively bound to serum proteins.
Metformin may decrease the anticoagulant effect of phenprocoumon. Therefore, a close monitoring of the INR is recommended.
Levothyroxine can reduce the hypoglycemic effect of metformin. Monitoring of blood glucose levels is recommended, especially when thyroid hormone therapy is initiated or stopped, and the dosage of metformin must be adjusted if necessary.
Organic caution 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, trimethoprim, 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 coadministered 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.