Note: This document contains side effect information about rosiglitazone. Some dosage forms listed on this page may not apply to the brand name Avandia.
Summary
Common side effects of Avandia include: headache. Other side effects include: edema and nausea. Continue reading for a comprehensive list of adverse effects.
Applies to rosiglitazone: oral tablets.
Warning
-
Congestive Heart Failure
- Thiazolidinediones, including rosiglitazone, cause or exacerbate CHF in some patients.1 116 117 128 141 143 Monitor patients for signs and symptoms of CHF (e.g., excessive, rapid weight gain; dyspnea; and/or edema) after initiation of therapy and dosage titration.1 117 128 If CHF signs and symptoms develop, manage according to current standards of care; in addition, consider discontinuance or reduction in dosage of rosiglitazone.1 117 128
- Not recommended in patients with symptomatic heart failure.1 113
- Initiation of rosiglitazone in patients with NYHA class III or IV heart failure contraindicated.1 128 (See Congestive Heart Failure under Cautions.)
Side effects include:
Upper respiratory tract infection, injury, headache.
For Healthcare Professionals
Applies to rosiglitazone: oral tablet.
General
The most commonly reported adverse reports included upper respiratory tract infections, injury, and headache.[Ref]
Cardiovascular
Major Adverse Cardiovascular Events:
Overall data from long-term rosiglitazone (the active ingredient contained in Avandia) trials including the RECORD, ADOPT, and DREAM trials (rosiglitazone n=6311; control n=7756) showed no difference in overall mortality or major adverse cardiovascular events; however, a meta-analysis of shorter-term trials suggests and increased risk for myocardial infarction with rosiglitazone compared with placebo.
The RECORD trial (Rosiglitazone evaluated for Cardiac Outcomes and Regulation of Glycemia in Diabetes) revealed no significant difference in cardiovascular hospitalization or cardiovascular death (primary outcome) among patients with type 2 diabetes receiving rosiglitazone add-on therapy (n=2220) compared with active control (n=2227); however, there was a significant difference in the incidence of CHF (secondary endpoint). Patients randomized were those who had failed metformin or sulfonylurea monotherapy; mean age: 58 years; 52% male. Following randomization to add-on rosiglitazone or active control (add-on metformin for those inadequately controlled on sulfonylurea or add-on sulfonylurea for those inadequately controlled on metformin) patients were treated to a target glycosylated hemoglobin (HbA1c) of 7% or less. Heart failure was reported in 61 patients receiving add-on rosiglitazone and 29 patients receiving active control.
In a retrospective analysis of 42 clinical trials (mean duration 6 months), rosiglitazone was associated with an increased risk of myocardial ischemia compared with combined active or placebo control (2% versus 1.53%). These events included angina pectoris, angina dyspnea, myocardial infarction, coronary thrombosis, myocardial ischemia, coronary artery disease, and coronary artery disorder. There was an increased risk with combination insulin therapy and in patients receiving nitrates for known coronary heart disease.
Cardiovascular Events in Patients with NYHA Class I and II Heart Failure:
An increased risk of cardiovascular events was observed in a 52-week trial in patients with NYHA Class I and II Heart Failure who were receiving rosiglitazone (n=110) compared with placebo (n=114). These events included: cardiovascular deaths (5% vs 4%), worsening CHF (6% vs 4%), new or worsening edema (25% vs 9%), new or worsening dyspnea (26% vs 17%), increases in CHF medication (33% vs 18%), and cardiovascular hospitalization (19% vs 13%).
Edema:
-Dose-related edema was reported in rosiglitazone clinical trials. In patients receiving rosiglitazone 8 mg in combination with a sulfonylurea, the incidence of edema was 12.4%. In rosiglitazone monotherapy trials, edema was reported in 4.8% of patients (dose not specified). Healthy volunteers receiving rosiglitazone 8 mg once daily for 8 weeks experienced a statistically significant increase in median plasma volume compared with placebo.
Concomitant Administration with Insulin:
-Edema was reported with higher frequency in the rosiglitazone plus insulin combination trials (insulin, 5.4%; and rosiglitazone with insulin 14.7%). Reports of new onset or exacerbation of CHF occurred at a rate of 1% for insulin alone, 2% (4 mg) and 3% (8 mg) for insulin in combination with rosiglitazone. The coadministration of rosiglitazone and insulin is not recommended.[Ref]
Common (1% to 10%): Edema, hypertension,
Frequency not reported: Cardiovascular deaths, congestive heart failure (CHF), myocardial infarction, angina, angina pectoris, angina dyspnea, myocardial infarction, coronary thrombosis, myocardial ischemia, coronary artery disease, coronary artery disorder[Ref]
Hematologic
Anemia was reported in 1.9% of patients receiving rosiglitazone (the active ingredient contained in Avandia) as monotherapy. In combination therapy with metformin, a sulfonylurea, or metformin plus a sulfonylurea, the incidence of anemia was 7.1%, 2.3%, and 6.7%, respectively. Laboratory findings have shown dose-related decreases in hemoglobin and hematocrit; mean decreases in hemoglobin were 1 g/dL and up to 3.3% in hematocrit. These changes primarily occurred during the first 3 months or following a dose increase. They may be related to increased plasma volume.[Ref]
Common (1% to 10%): Anemia
Frequency not reported: Decrease in WBC counts[Ref]
Hepatic
Uncommon (0.1% to 1%): Hyperbilirubinemia, ALT elevations
Postmarketing reports: Hepatitis, hepatic enzyme elevations greater than 3 times the upper limit of normal, hepatic failure[Ref]
Metabolic
Common (1% to 10%): Hyperglycemia, hypoglycemia, hypocholesterolemia
Uncommon (0.1% to 1%): Weight gain
Frequency not reported: Increases in waist and hip circumference[Ref]
The mechanism of weight gain is unclear, although it probably is due to a combination of fluid retention and fat accumulation. In the ADOPT monotherapy trial, median weight change at 4 years was plus 3.5 kg.[Ref]
Endocrine
Frequency not reported: Resumption of ovulation in premenopausal, anovulatory women, hormonal imbalance[Ref]
Hypersensitivity
Postmarketing reports: Anaphylactic reaction, urticaria, angioedema[Ref]
Dermatologic
Postmarketing reports: Rash, pruritus, urticaria, angioedema, Stevens-Johnson syndrome[Ref]
Ocular
Postmarketing reports: Diabetic macular edema with decreased visual acuity[Ref]
Respiratory
Common (1% to 10%): Upper respiratory tract infection, sinusitis
Frequency not reported: Dyspnea
Postmarketing reports: Pulmonary edema, pleural effusions[Ref]
Musculoskeletal
Long-term clinical trials have shown an increased incidence of bone fracture in patients receiving drug compared with glyburide or metformin. This increased incidence appeared after the first year and persisted during the trials. The majority of fractures were observed in women and occurred in the upper arm, hand, and foot.[Ref]
Common (1% to 10%): Back pain
Frequency not reported: Fractures[Ref]
Gastrointestinal
Common (1% to 10%): Diarrhea[Ref]
Other
Common (1% to 10%): Injury, fatigue[Ref]
