Trade Names:Avandaryl- Tablets rosiglitazone 4 mg/glimepiride 1 mg- Tablets rosiglitazone 4 mg/glimepiride 2 mg- Tablets rosiglitazone 4 mg/glimepiride 4 mg- Tablets rosiglitazone 8 mg/glimepiride 2 mg- Tablets rosiglitazone 8 mg/glimepiride 4 mg
Rosiglitazone, a thiazolidinedione, increases insulin sensitivity in the liver, skeletal muscle, and adipose tissues. Glimepiride, a sulfonylurea, stimulates insulin release from functioning pancreatic beta cells.
Adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes when treatment with dual rosiglitazone and glimepiride therapy is appropriate.
Known hypersensitivity to any component of the product; established New York Heart Association (NYHA) class III or IV heart failure.
PO Initial: Rosiglitazone 4 mg/glimepiride 1 mg or rosiglitazone 4 mg/glimepiride 2 mg once daily. Titrate to clinical response (max, rosiglitazone 8 mg/glimepiride 4 mg).Elderly, Debilitated, or Malnourished Patients, or Patients With Adrenal, Hepatic, or Renal Function Impairment
Initial dosing, dose increments, and maintenance dosage should be conservative to avoid hypoglycemia.Switching From Separate Doses of Rosiglitazone and Glimepiride to Combined TherapyAdults
PO Usual starting dose is the dose of rosiglitazone and glimepiride already being taken.Patients Previously Treated With Thiazolidinedione Monotherapy and Switching to Combined TherapyAdults
PO Dose titration can occur at 1- to 2-wk intervals by increasing the glimepiride component by no more than 2 mg increments.Patients Previously Treated With Sulfonylurea Monotherapy and Switching to Combined TherapyAdults
PO Full effect of rosiglitazone component on glucose reduction may take 2 to 3 mo to develop. Titration of the rosiglitazone component is recommended if patients are not adequately controlled after 8 to 12 wk. Observe patients for 1 to 2 wk for hypoglycemia when being transferred from longer half-life sulfonylureas (eg, chlorpropamide) because of potential overlapping drug effect. Dosage titration of the rosiglitazone component is recommended if patient is not adequately controlled after 2 to 3 mo. Increases in rosiglitazone dose should be accompanied by careful monitoring for adverse reactions related to fluid retention.Hepatic Function ImpairmentAdults
PO Treatment should not be initiated in patients exhibiting evidence of active liver disease or increased serum transaminase levels (ALT more then 2.5 × ULN at the start of therapy).
Store tablets at 59° to 86°F. Protect from light.
Risk of hypoglycemia may be increased.Alcohol
Disulfiram-like reactions (eg, breathlessness, facial flushing, headache) may occur.Ciprofloxacin, gatifloxacin
Severe and persistent hypoglycemia may occur.CYP2C8 inducers (eg, rifampin)
May reduce rosiglitazone plasma levels, decreasing the pharmacologic effects.CYP2C8 inhibitors (eg, azole antifungal agents [ketoconazole], fluvoxamine, gemfibrozil, trimethoprim)
May elevate rosiglitazone plasma levels, increasing the pharmacologic effects and adverse reactions.Drugs that cause hyperglycemia (eg, corticosteroids, diazoxide, diuretics, estrogens, isoniazid, nicotinic acid, oral contraceptives, phenothiazines, phenytoin, sympathomimetics, thyroid products)
May lead to loss of glycemic control.Drugs that cause hypoglycemia (eg, beta-adrenergic blockers, chloramphenicol, fluconazole, MAOIs, miconazole, NSAIDs, probenecid, salicylates, sulfinpyrazone, sulfonamides, urine acidifiers)
May lead to loss of glycemic control.Insulin
Risk of edema may be increased, even after several months of combined therapy.Nevirapine
Nevirapine plasma concentrations may be reduced, decreasing efficacy.
None well documented.
Hypertension (3%); CHF (postmarketing).
Pruritus, rash, Stevens-Johnson syndrome, urticaria (postmarketing).
Nasopharyngitis (5%); decreased visual acuity, new-onset or worsening diabetic macular edema (postmarketing).
Hepatic enzyme elevations, hepatic failure, hepatitis (postmarketing).
Anaphylactic reaction, angioedema (postmarketing).
Pleural edema, pulmonary effusions (postmarketing).
Edema (3%); fractures.
May occur or be exacerbated. Observe patients for signs and symptoms of heart failure after starting therapy or increasing the dose. Manage heart failure according to current standards of care. Consider discontinuation or dose reduction if signs or symptoms occur. Use of drug is not recommended in patients with symptomatic heart failure. Use of drug is contraindicated in patients with NYHA class III or IV CHF.Myocardial ischemia
Rosiglitazone is associated with an increased risk of myocardial ischemic events (eg, angina, MI). However, available data on this risk are inconclusive.
Obtain periodic fasting blood glucose and hemoglobin A 1c (HbA 1c ) concentrations to monitor therapeutic response. Assess liver enzymes prior to initiation of therapy and periodically thereafter. Monitor all patients for signs and symptoms associated with fluid retention (eg, edema, heart failure).
Category C . Not recommended during pregnancy.
Safety and efficacy not established.
Particularly susceptible to hypoglycemic action. In general, do not titrate to the max dose because of age-related decreases in renal function.
Do not initiate therapy in patients with clinical evidence of active liver disease or baseline ALT more than 2.5 × ULN. Initiation or continuation of therapy in patients with mildly elevated liver enzymes (ALT less than 2.5 × ULN) should proceed with caution; discontinue therapy in these patients if ALT increases to more than 3 × ULN and persists.
Increased incidence of bone fractures noted in women, but not in men.
The addition of rosiglitazone to insulin therapy increased the risk of CHF and myocardial ischemia. Coadministration is not recommended.
Has occurred in patients treated with oral hypoglycemic drugs.
Rosiglitazone may cause fluid retention. Use with caution in patients with edema or at risk of heart failure.
Stabilized patients exposed to stress (eg, fever, trauma, infection, surgery) may experience a temporary loss of glycemic control. In this instance, it may be necessary to withhold treatment and temporarily give insulin.
Dose-related decreases in Hgb and Hct have been reported in patients taking rosiglitazone.
May produce severe hypoglycemia. Debilitated or malnourished patients, and those with adrenal, pituitary, renal, or hepatic insufficiency are particularly susceptible.
New-onset or worsening macular edema with decreased visual acuity has been reported rarely in patients receiving rosiglitazone.
Rosiglitazone therapy may result in resumption of ovulation in premenopausal anovulatory women with insulin resistance. Consider contraceptive measures in such patients.
Do not use in these patients.
Dose-related weight gain has been reported. Assess patients who experience unusually rapid increases in weight for fluid accumulation and volume-related events (eg, edema, heart failure).
Hypoglycemic reactions with coma, seizures, or other neurological impairment.
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