Trade Names:Avandamet- Tablets rosiglitazone 2 mg/metformin 500 mg- Tablets rosiglitazone 2 mg/metformin 1,000 mg- Tablets rosiglitazone 4 mg/metformin 500 mg- Tablets rosiglitazone 4 mg/metformin 1,000 mg
Increases insulin sensitivity.Metformin
Decreases blood glucose by reducing hepatic glucose production, increases peripheral glucose uptake and utilization, and decreases intestinal absorption of glucose.
Plasma and blood half-life of metformin is prolonged and the renal Cl is decreased in proportion to the decrease in CrCl.Hepatic Function Impairment
Cl of rosiglitzone was significantly lower in patients with moderate to severe liver disease and C max and AUC 0-∞ were increased 2- and 3-fold, respectively.
As an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus when treatment with combination rosiglitazone and metformin is appropriate.
Patients with renal disease or renal function impairment that may also result from conditions such as CV collapse, acute MI, and septicemia; acute or chronic metabolic acidosis, with or without coma; known hypersensitivity to any component of the product; established New York Heart Association class III or IV heart failure; temporarily suspend treatment in patients undergoing radiologic studies involving intravascular administration of iodinated contrast materials.
Base dosage selection of rosiglitazone and metformin on the patient's current doses of rosiglitazone or metformin (max daily dose, rosiglitazone 8 mg/metformin 2,000 mg).Patients Inadequately Controlled on Metformin MonotherapyAdults
PO Start with rosiglitazone 4 mg daily plus the metformin dose already being taken. If prior therapy consists of metformin 1,000 mg/day, start with 2 mg/500 mg and administer 1 tablet twice daily. If prior therapy consists of metformin 2,000 mg/day, start with 2 mg/1,000 mg and administer 1 tablet twice daily.Patients Inadequately Controlled on Rosiglitazone MonotherapyAdults
PO Start with metformin 1,000 mg daily plus the rosiglitazone dose already being taken. If prior therapy consists of rosiglitazone 4 mg/day, start with 2 mg/500 mg and administer 1 tablet twice daily. If prior therapy consists of rosiglitazone 8 mg/day, start with 4 mg/500 mg and administer 1 tablet twice daily.Switching from Separate Doses of Rosiglitazone and Metformin to Combination TherapyAdults
PO Start with the doses of rosiglitazone and metformin already being taken. Increase the dose in increments of rosiglitazone 4 mg and/or metformin 500 mg up to the max recommended total daily dose of 8 mg/2,000 mg.Drug-Naive PatientsAdults
PO Start with 2 mg/500 mg once or twice daily. Consider a starting dosage of 2 mg/500 mg twice daily for patients with glycosylated hemoglobin (HbA 1c ) more than 11% or fasting plasma glucose more than 270 mg/dL. Increase dose in increments of 2 mg/500 mg per day in divided doses if patient is not adequately controlled after 4 wk (max, 8 mg/2,000 mg per day).Renal Function ImpairmentAdults
PO Dosage adjustments should be based on careful assessment of renal function.Hepatic Function ImpairmentAdults
PO Do not initiate treatment in patients exhibiting evidence of active liver disease or increased serum transaminase levels (ALT more than 2.5 × ULN at the start of therapy).
Store at 59° to 86°F. Protect from light.
The effects of metformin on lactate metabolism may be potentiated.Cationic drugs (eg, amiloride, cimetidine, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, vancomycin)
Use with caution; may interact with metformin by competing for common renal tubular transport systems.Cimetidine
Increased metformin plasma levels.CYP2C8 inducers (eg, rifampin)
Rosiglitazone plasma concentrations may be reduced, decreasing the efficacy.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, calcium channel blockers, corticosteroids, 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, NSAIDs, probenecid, salicylates, sulfinpyrazone, sulfonamides, urine acidifiers)
May lead to loss of glycemic control.Furosemide
Metformin plasma levels may be elevated while furosemide levels may be decreased.Insulin
Risk of edema may be increased, even after several months of therapy.Iodinated contrast material
May cause acute renal failure and has been associated with lactic acidosis in patients receiving metformin.Nevirapine
Nevirapine plasma concentrations may be reduced, decreasing efficacy.Nifedipine
Metformin plasma levels may be increased.
None well documented.
Headache (11%); dizziness (8%); fatigue (6%).
Pruritus, rash, Stevens-Johnson syndrome, urticaria (postmarketing).
Nasopharyngitis (6%); decreased visual acuity, diabetic macular edema (postmarketing).
Nausea/vomiting (16%); diarrhea (14%); dyspepsia (10%); abdominal pain, constipation, loose stools (5%).
Anemia (7%); decreased Hgb and Hct.
Hepatic failure, hepatitis and hepatic enzyme elevations (postmarketing).
Hypoglycemia (12%); edema (6%).
Arthralgia, back pain (5%).
Upper respiratory tract infection (16%); sinusitis (6%); pulmonary edema, pulmonary effusions (postmarketing).
Injury (8%); viral infection (5%); anaphylactic reaction, angioedema (postmarketing).
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 develop. Use of drug is not recommended in patients with symptomatic heart failure.Lactic acidosis
Lactic acidosis is a rare but serious metabolic complication that can occur because of metformin accumulation during treatment with rosiglitazone/metformin. It is fatal in approximately 50% of cases.Myocardial ischemia
Rosiglitazone is associated with an increased risk of myocardial ischemic events (eg, angina, MI). However, available data on the risk of myocardial ischemia are inconclusive.
Monitor all patients, especially those receiving rosiglitazone concurrently with a sulfonylurea or insulin and those at risk of heart failure or with mild to moderate heart failure, for signs and symptoms relating to fluid retention, including heart failure. Because the risk of metformin accumulation and lactic acidosis increases with the degree of renal function impairment, assess renal function before starting therapy and at least annually thereafter. Discontinue rosiglitazone/metformin if there is evidence of renal function impairment. Measure fasting blood glucose and HbA 1c periodically to monitor therapeutic response. Initial and periodic monitoring of liver enzymes, hematologic parameters, and renal function is recommended.
Category C .
Safety and efficacy not established.
In general, elderly patients are not titrated to the max dose because of age-related decreases in renal function.
Decreased renal function results in decreased renal Cl and prolongation of the metformin half-life. Concomitant medications that affect renal function may result in hemodynamic changes or interfere with disposition of metformin (eg, cationic drugs); use with caution. Avoid metformin in patients whose serum creatinine levels exceed the ULN for their age.
Avoid metformin in patients with clinical or laboratory evidence of hepatic disease.
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 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.
Do not titrate elderly, debilitated, and malnourished patients to the max dose. Use with caution in patients with edema; avoid use in patients with type 1 diabetes.
Increased incidence of bone fractures has been noted in women taking rosiglitazone, but not men.
Promptly evaluate patients who develop laboratory abnormalities or clinical illness for evidence of ketoacidosis or lactic acidosis. Evaluate serum electrolytes and ketones, blood glucose, and, if indicated, blood pH, lactate, pyruvate, and metformin concentrations.
The addition of rosiglitazone to insulin therapy increased the risk of CHF and myocardial ischemia. Coadministration is not recommended.
Rosiglitazone may cause fluid retention; use with caution in patients with edema or those who are at risk of heart failure.
Dose-related decreases in HgB and Hct have been reported in patients taking rosiglitazone.
Risk may be increased when used in combination with other hypoglycemic agents, necessitating dose reduction of concomitant therapy.
Immediately discontinue therapy in any condition characterized by hypoxemia (eg, acute CHF, MI).
Withhold metformin therapy at the time of or prior to parenteral contrast studies with iodinated materials. Reinstitute therapy 48 h after the study and after renal function has been determined to be healthy.
Can occur as a result of metformin accumulation (eg, renal function impairment) or in pathophysiologic conditions associated with tissue hypoperfusion and hypoxia. The risk of lactic acidosis increases with the degree of renal function impairment and the age of the patient.
Has been reported in postmarketing experience in patients taking rosiglitazone.
Rosiglitazone therapy may result in ovulation in some premenopausal anovulatory women, increasing the risk of pregnancy.
Treatment should be temporarily suspended for any surgical procedure, except minor procedures not associated with restricted intake of food and fluids, and should not be restarted until oral intake has resumed and renal function has been evaluated as normal.
Not indicated for use in patients with type 1 diabetes.
Metformin may decrease vitamin B 12 levels.
Dose-related weight gain was seen with rosiglitazone.
Copyright © 2009 Wolters Kluwer Health.