Glimepirideinteractions

Strong CYP2C8 inhibitors (e.g., gemfibrozil) increase pioglitazone concentrations. Limit pioglitazone dose to 15 mg daily. CYP2C8 inducers (e.g., rifampin) may decrease pioglitazone concentrations. Topiramate may decrease pioglitazone concentrations. Certain medications may affect glucose metabolism, requiring pioglitazone and glimepiride tablet dose adjustment and close monitoring of blood glucose.

Miconazole: Severe hypoglycemia can occur when pioglitazone and glimepiride tablets and oral miconazole are used concomitantly.

CYP2C9 interactions: Inhibitors and inducers may affect glycemic control by altering glimepiride plasma concentrations.

Colesevelam: Coadministration may reduce glimepiride absorption. Pioglitazone and glimepiride tablets should be administered at least 4 hours prior to colesevelam.

7.1 Strong CYP2C8

Inhibitors Pioglitazone An inhibitor of CYP2C8 (e.g., gemfibrozil) significantly increases the exposure (area under the serum concentration-time curve or AUC) and half-life (t ½ ) of pioglitazone. Therefore, the maximum recommended dose of pioglitazone is 15 mg daily if used in combination with gemfibrozil or other strong CYP2C8 inhibitors. Since the minimum dose of pioglitazone in pioglitazone and glimepiride tablets exceeds 15 mg, patients taking concomitant strong CYP2C8 inhibitors should switch to individual components of pioglitazone and glimepiride tablets, unless the prescribing health care provider determines that the benefit of pioglitazone and glimepiride tablets clearly outweighs the risk of increased pioglitazone exposure.

7.2 CYP2C8 Inducers

Pioglitazone An inducer of CYP2C8 (e.g., rifampin) may significantly decrease the exposure (AUC) of pioglitazone. Therefore, if an inducer of CYP2C8 is started or stopped during treatment with pioglitazone, changes in diabetes treatment may be needed based on clinical response without exceeding the maximum recommended daily dose of 45 mg for pioglitazone.

7.3 Topiramate

Pioglitazone A decrease in the exposure of pioglitazone and its active metabolites were noted with concomitant administration of pioglitazone and topiramate. The clinical relevance of this decrease is unknown; however, when pioglitazone and topiramate are used concomitantly, monitor patients for adequate glycemic control.

7.4 Drugs Affecting

Glucose Metabolism Glimepiride A number of medications affect glucose metabolism and may require pioglitazone and glimepiride tablet dose adjustment and particularly close monitoring for hypoglycemia or worsening glycemic control. The following are examples of medications that may increase the glucose-lowering effect of sulfonylureas including glimepiride, a component of pioglitazone and glimepiride tablets, increasing the susceptibility to and/or intensity of hypoglycemia: oral anti-diabetic medications, pramlintide acetate, insulin, angiotensin converting enzyme (ACE) inhibitors, H2 receptor antagonists, fibrates, propoxyphene, pentoxifylline, somatostatin analogs, anabolic steroids and androgens, cyclophosphamide, phenyramidol, guanethidine, fluconazole, sulfinpyrazone, tetracyclines, clarithromycin, disopyramide, quinolones, and those drugs that are highly protein-bound, such as fluoxetine, nonsteroidal anti-inflammatory drugs, salicylates, sulfonamides, chloramphenicol, coumarins, probenecid and monoamine oxidase inhibitors. When these medications are administered to a patient receiving pioglitazone and glimepiride tablets, monitor the patient closely for hypoglycemia. When these medications are withdrawn from a patient receiving pioglitazone and glimepiride tablets, monitor the patient closely for worsening glycemic control. The following are examples of medications that may reduce the glucose-lowering effect of sulfonylureas including glimepiride, leading to worsening glycemic control: danazol, glucagon, somatropin, protease inhibitors, atypical antipsychotic medications (e.g., olanzapine and clozapine), barbiturates, diazoxide, laxatives, rifampin, thiazides and other diuretics, corticosteroids, phenothiazines, thyroid hormones, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics (e.g., epinephrine, albuterol, terbutaline), and isoniazid. When these medications are administered to a patient receiving pioglitazone and glimepiride tablets, monitor the patient closely for worsening glycemic control. When these medications are withdrawn from a patient receiving pioglitazone and glimepiride tablets, monitor the patient closely for hypoglycemia. Beta-blockers, clonidine, and reserpine may lead to either potentiation or weakening of pioglitazone and glimepiride tablets glucose-lowering effect. Both acute and chronic alcohol intake may potentiate or weaken the glucose-lowering action of pioglitazone and glimepiride tablets in an unpredictable fashion. The signs of hypoglycemia may be reduced or absent in patients taking sympatholytic drugs such as beta-blockers, clonidine, guanethidine, and reserpine.

7.5 Miconazole

Glimepiride A potential interaction between oral miconazole and sulfonylureas leading to severe hypoglycemia has been reported. Whether this interaction also occurs with other dosage forms of miconazole is not known.

7.6 CYP2C9 Interactions

Glimepiride There may be an interaction between glimepiride and inhibitors (e.g., fluconazole) and inducers (e.g., rifampin) of CYP2C9. Fluconazole may inhibit the metabolism of glimepiride, causing increased plasma concentrations of glimepiride which may lead to hypoglycemia. Rifampin may induce the metabolism of glimepiride, causing decreased plasma concentrations of glimepiride which may lead to worsening glycemic control.

7.7 Concomitant

Administration of Colesevelam Glimepiride Colesevelam can reduce the maximum plasma concentrations and total exposure of glimepiride when the two are coadministered. However, absorption is not reduced when glimepiride is administered four hours prior to colesevelam. Therefore, pioglitazone and glimepiride tablets should be administered at least four hours prior to colesevelam.