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 and Warnings and Precautions .]
- 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 .]
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 .]
- 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 .]
- If acidosis is suspected, discontinue AVANDAMET and hospitalize the patient immediately [see Warnings and Precautions].
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.
Media Articles Related to Avandamet (Rosiglitazone)
Avandia (Rosiglitazone) Does Not Raise Heart Attack Risk, Study
Source: Cardiovascular / Cardiology News From Medical News Today [2013.06.07]
There is not a higher risk of heart attack and cardiovascular events in patients who take controversial type 2 drug Avandia (rosiglitazone), researchers at the Duke Clinical Research Institute (DCRI) reported after carrying out a re-analysis of data from a pivotal study...
Restrictions On Avandia (Rosiglitazone) Should Be Loosened, Says FDA Panel
Source: Diabetes News From Medical News Today [2013.06.07]
Most of the 26-member advisory FDA panel voted to loosen the restrictions which were placed on GSK's diabetes drug Avandia (rosiglitazone) in 2010 because of concerns it might raise the risk of heart attacks and death from cardiovascular causes...
Insulin Sensitizers Halve PAD Risk, Amputations in BARI 2D
Source: Medscape Diabetes & Endocrinology Headlines [2013.06.10]
The same week that 2 FDA panels voted to keep rosiglitazone on the market, a new analysis from BARI 2D finds that insulin sensitizers such as this lower PAD risk in patients with diabetes and CAD.
Medscape Medical News
Avandia's Future Still Bleak?
Source: MedPage Today Nephrology [2013.06.07]
(MedPage Today) -- An FDA panel recommendation to loosen restrictions on the diabetes drug rosiglitazone (Avandia) isn't likely to affect how -- or whether -- doctors prescribe it, according to experts interviewed by MedPage Today.
Published Studies Related to Avandamet (Rosiglitazone)
Rosiglitazone decreases plasma levels of osteoprotegerin in a randomized clinical trial with type 2 diabetes patients. [2011.12]
Cardiovascular disease is the leading cause of death in patients with type 2 diabetes mellitus (T2DM). We suggested that plasma osteoprotegerin (OPG), a strong, independent predictor of cardiovascular disease, could discriminate between anti-diabetic treatments depending on their benefits regarding cardiovascular disease...
Rosiglitazone decreases fasting plasma peptide YY(3-36) in type 2 diabetic women: a possible role in weight gain? [2011.11.19]
Rosiglitazone often results in weight gain. We hypothesized that rosiglitazone may modulate circulating levels of ghrelin and peptide YY(3-36) and this modulation may be related to weight-gaining effect of this agent... Rosiglitazone-induced decrease in fasting peptide YY(3-36) levels may in part contribute to orexigenic and weight-gaining effect of this thiazolidinedione derivative.
Rosiglitazone and pioglitazone for the treatment of Alzheimer's disease. [2011.11]
CONCLUSIONS: Results from clinical trials and current safety data suggest that rosiglitazone should not be used for the treatment of AD. Application of results from trials evaluating pioglitazone in the treatment of AD is limited because of major trial limitations; therefore, it should not be recommended at this time. Although these drugs are not commonly used in the treatment of AD, further pharmacoepidemiologic studies are warranted before their use can be recommended.
Effect of lifestyle intervention plus rosiglitazone or placebo therapy on left ventricular mass assessed with cardiovascular magnetic resonance in the metabolic syndrome. [2011.10.28]
ABSTRACT: BACKGROUND: To evaluate the effect of lifestyle intervention in conjunction with rosiglitazone or placebo therapy on left ventricular (LV) mass, using cardiovascular magnetic resonance (CMR) in the metabolic syndrome... CONCLUSIONS: Lifestyle intervention resulted in a reduction of LV mass-I in the metabolic syndrome, indicating reverse remodeling. However, rosiglitazone therapy may have inhibited this positive reverse remodeling. TRIAL REGISTRATION: Current Controlled Trials ISRCTN54951661.
A randomized controlled trial of the effect of rosiglitazone and clomiphene citrate versus clomiphene citrate alone in overweight/obese women with polycystic ovary syndrome. [2011.10.04]
Background: In women suffering from polycystic ovary syndrome, correction of hyperinsulinemia results in enhanced responsiveness to ovulation induction agents. The effect of rosiglitazone was investigated on ovulation induction in obese women with PCOS... Conclusions: Short term administration of rosiglitazone to overweight and obese PCOS women results in enhancement of CC induced ovulation as well as improvement of insulin sensitivity.
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.
Rosiglitazone and Metformin: Outcomes Trial in Nondiabetic Patients With Stable Coronary Syndromes (Romance) Pilot Study [Recruiting]
Nearly half of all Americans will die from cardiovascular disease caused by the build up of
atherosclerotic plaque within coronary arteries. Most deaths in these patients arise from
the development of acute coronary syndromes (ACS) such as myocardial infarction, unstable
angina, or sudden death. ACS is characterized by coronary plaque erosion or rupture, which
is triggered by endothelial changes, including inflammation, and thrombosis. Diabetes, with
insulin resistance as a major component, has been shown to engender adverse metabolic events
within the endothelial cell , including impaired endothelial function, augmented
vasoconstriction, increased inflammation and thrombosis. Activation of the transcription
factors nuclear factor KB (NF-KB) and activator protein 1 (AP-1) induces inflammatory gene
expression, with liberation of leukocyte-attracting chemokines, increased production of
inflammatory cytokines, and augmented expression of cellular adhesion molecules. These
metabolic processes may therefore play a significant role in the development of ACS. The
hypothesis is that rosiglitazone and metformin, or the combination of both may provide
positive anti-atherogenic effect, even among patients without diabetes. This pilot study
proposes to evaluate the effect of placebo vs. combined rosiglitazone/metformin (Avandamet®)
on surrogate blood markers of atherosclerosis activity among non-diabetic and pre-diabetic
patients with known stable coronary syndromes. This will provide further evidence
justifying a large definitive outcomes-based clinical trial.
Reports of Suspected Avandamet (Rosiglitazone) Side Effects
Myocardial Infarction (617),
Cardiac Failure Congestive (445),
Coronary Artery Disease (319),
Cerebrovascular Accident (312),
Cardiac Disorder (195),
Cardiovascular Disorder (157),
Chest Pain (100),
Transient Ischaemic Attack (79),
Atrial Fibrillation (73), more >>
Page last updated: 2013-06-10