WARNINGS
Rosiglitazone maleate: CONGESTIVE HEART FAILURE AND MYOCARDIAL ISCHEMIA
- Thiazolidinediones, including rosiglitazone, cause or exacerbate congestive heart failure in some patients [see Warnings and Precautions]. After initiation of AVANDAMET, and after dose increases, observe patients carefully for signs and symptoms of heart failure (including excessive, rapid weight gain, dyspnea, and/or edema). If these signs and symptoms develop, the heart failure should be managed according to current standards of care. Furthermore, discontinuation or dose reduction of AVANDAMET must be considered.
- AVANDAMET is not recommended in patients with symptomatic heart failure. Initiation of AVANDAMET in patients with established NYHA Class III or IV heart failure is contraindicated. [See Contraindications (4) and Warnings and Precautions (5.2).]
- A meta-analysis of 42 clinical studies (mean duration 6 months; 14,237 total patients), most of which compared rosiglitazone to placebo, showed rosiglitazone to be associated with an increased risk of myocardial ischemic events such as angina or myocardial infarction. Three other studies (mean duration 41 months; 14,067 total patients), comparing rosiglitazone to some other approved oral antidiabetic agents or placebo, have not confirmed or excluded this risk. In their entirety, the available data on the risk of myocardial ischemia are inconclusive. [See Warnings and Precautions (5.3).]
Metformin hydrochloride: LACTIC ACIDOSIS
- Lactic acidosis is a rare, but serious complication that can occur due to metformin accumulation. The risk increases with conditions such as sepsis, dehydration, excess alcohol intake, hepatic insufficiency, renal impairment, and acute congestive heart failure. [See Warnings and Precautions (5.1).]
- Symptoms include malaise, myalgias, respiratory distress, increasing somnolence, and nonspecific abdominal distress. Laboratory abnormalities include low pH, increased anion gap and elevated blood lactate. [See Warnings and Precautions (5.1).]
- If acidosis is suspected, discontinue AVANDAMET and hospitalize the patient immediately [see Warnings and Precautions].
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AVANDAMET SUMMARY
AVANDAMET (rosiglitazone maleate and metformin HCl) tablets contain 2 oral antihyperglycemic drugs used in the management of type 2 diabetes: Rosiglitazone maleate and metformin hydrochloride. The combination of rosiglitazone maleate and metformin hydrochloride has been previously approved based on clinical trials in people with type 2 diabetes mellitus inadequately controlled on metformin alone. Additional efficacy and safety information about rosiglitazone and metformin monotherapies may be found in the prescribing information for each individual drug.
AVANDAMET is indicated as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus who are already treated with combination rosiglitazone and metformin or who are not adequately controlled on metformin alone.
Management of type 2 diabetes mellitus should include diet control. Caloric restriction, weight loss, and exercise are essential for the proper treatment of the diabetic patient because they help improve insulin sensitivity. This is important not only in the primary treatment of type 2 diabetes but also in maintaining the efficacy of drug therapy. Prior to initiation or escalation of oral antidiabetic therapy in patients with type 2 diabetes mellitus, secondary causes of poor glycemic control, e.g., infection, should be investigated and treated.
The safety and efficacy of AVANDAMET as initial pharmacologic therapy for patients with type 2 diabetes mellitus after a trial of caloric restriction, weight loss, and exercise has not been established.
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NEWS HIGHLIGHTS
Published Studies Related to Avandamet (Rosiglitazone)
A multicentre, randomized, double-blind placebo-controlled trial evaluating rosiglitazone for the prevention of atherosclerosis progression after coronary artery bypass graft surgery in patients with type 2 diabetes. Design and rationale of the VeIn-Coronary aTherOsclerosis and Rosiglitazone after bypass surgerY (VICTORY) trial. [2009.09]
BACKGROUND: The number of patients with coronary artery disease and type 2 diabetes will increase dramatically over the next decade. Diabetes has been related to accelerated atherosclerosis and many patients with diabetes will require coronary artery bypass graft (CABG) surgery utilizing saphenous vein grafts. After CABG, accelerated atherosclerosis in saphenous vein grafts leads to graft failure in approximately 50% of cases over a 10-year period. Rosiglitazone, a peroxisome proliferator-activated receptor-gamma agonist, has been shown to improve multiple metabolic parameters in patients with type 2 diabetes. However, its role in the prevention of atherosclerosis progression is uncertain... CONCLUSIONS: The VICTORY trial is the first cardiometabolic study to evaluate the antiatherosclerotic and metabolic effects of rosiglitazone in post-CABG patients with type 2 diabetes.
Twice-daily dosing of a repaglinide/metformin fixed-dose combination tablet provides glycaemic control comparable to rosiglitazone/metformin tablet. [2009.09]
AIM: To assess the use of a new repaglinide/metformin fixed-dose combination (FDC) tablet for the treatment of type 2 diabetes... CONCLUSIONS: The repaglinide/metformin FDC BID regimen showed efficacy that was non-inferior to that of the rosiglitazone/metformin FDC BID regimen currently in clinical use and a more rapid reduction of HbA1c values. Thus, repaglinide/metformin FDC BID is a clinically feasible alternative to rosiglitazone/metformin FDC BID.
A rosiglitazone-induced increase in adiponectin does not improve glucose metabolism in HIV-infected patients with overt lipoatrophy. [2009.08.18]
HIV-infected patients on antiretroviral therapy frequently develop changes in body fat distribution and disturbances in glucose metabolism, associated with reduced adiponectin levels. As adiponectin, principally the HMW (high-molecular-weight) form, has insulin sensitizing properties, we investigated the effects of an increase in adiponectin on glucose metabolism in HIV-lipodystrophy...
Effect of rosiglitazone on progression of atherosclerosis: insights using 3D carotid cardiovascular magnetic resonance. [2009.07.27]
CONCLUSION: Treatment with rosiglitazone over 1 year had no effect on progression of carotid atheroma in patients with type 2 diabetes mellitus compared to placebo.
Impact of rosiglitazone and glyburide on nitrosative stress and myocardial blood flow regulation in type 2 diabetes mellitus. [2009.07]
Cardiovascular disease, the leading cause of death in patients with type 2 diabetes mellitus (T2DM), is usually preceded by endothelial dysfunction and altered myocardial blood flow (MBF) regulation... Rosiglitazone, but not glyburide, ameliorated markers of nitrosative stress and inflammation in subjects with T2DM without impairing myocardial perfusion.
Clinical Trials Related to Avandamet (Rosiglitazone)
AVANDAMET Versus Metformin And Sulphonylurea In People With Poorly Controlled Type 2 Diabetes [Completed]
This study compares the effects of Avandamet (rosiglitazone maleate/metformin) treatment and
metformin plus sulphonylurea treatment in overweight people with type 2 diabetes.
AVANDAMET Versus Metformin For Type 2 Diabetes Mellitus [Completed]
This 48-week study will compare AVANDAMET vs. Metformin monotherapy for blood glucose control
in patients with Type 2 Diabetes Mellitus.
Study Of AVANDAMET With Or Without Insulin In Type II Diabetes Mellitus Patients [Completed]
This study was designed to test the safety and efficacy (how well it works) of AVANDAMET in
combination with insulin in improving the control of blood sugar when compared with taking
insulin on its own. AVANDAMET capsules contain a fixed dose of AVANDIA and metformin. Both
AVANDIA and metformin are medicines which are individually licensed for the treatment of type
II diabetes mellitus. Because they act in different ways, it is thought that combining them
may give an increased benefit of treating diabetes and reducing blood sugar.
Avandia™ + Amaryl™ or Avandamet™ Compared With Metformin (AVALANCHE™ Study) [Completed]
The incidence of type 2 diabetes is on the increase. According to recent Canadian Diabetes
Association guidelines glucose control, based on the A1C measurement, needs to be achieved
within a 6-12 month period of time after the initial diagnosis of type 2 diabetes. The
guidelines on the use of antihyperglycemic agents identify the potential benefits of
sub-maximal oral combination therapy in order to achieve more rapid and improved glycemic
control compared with higher dose monotherapy. Furthermore, many patients on prolonged oral
antihyperglycemic monotherapy who then start on combination therapy may not achieve the
required target glycemic control. Indeed early initiation of combination therapies may be
necessary to achieve and maintain glycemic targets because of the progressive deterioration
of pancreatic β cell function and glycemic control.
A Type 2 Diabetes Study of the Longer-Term Glycemic Effect of AVANDAMET vs. Metformin [Recruiting]
This study will evaluate the longer-term glycemic effect of two medicines approved for
initial treatment of type 2 diabetes. The study consists of a 2 week screening period (2
study visits), followed by an 80 week double-blind treatment period (11 study visits).
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Page last updated: 2009-10-20
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