Note: This document contains side effect information about glimepiride / rosiglitazone. Some dosage forms listed on this page may not apply to the brand name Avandaryl.
Applies to glimepiride / rosiglitazone: oral tablet.
Endocrine
Frequency not reported: Resumption of ovulation in premenopausal, anovulatory women, hormonal imbalance[Ref]
Cardiovascular
Major Adverse Cardiovascular Events:
Overall data from rosiglitazone long-term 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; mean age 58 years; 52% male) 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 congestive heart failure (secondary endpoint). Patients who had failed metformin or sulfonylurea monotherapy were randomized 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 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 monotherapy trials, edema was reported in 4.8% of patients receiving rosiglitazone (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 congestive heart failure 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]
Glimepiride-Rosiglitazone:
Common (1% to 10%): Edema, hypertension
Uncommon (0.1% to 1%): Congestive heart failure
Glimepiride: Common (1% to 10%): Edema, hypertension
Rosiglitazone:
Common (1% to 10%): Edema, hypertension
Uncommon (0.1% to 1%): Congestive heart failure
Frequency not reported: Cardiovascular deaths, myocardial infarction, angina, angina pectoris, angina dyspnea, myocardial infarction, coronary thrombosis, myocardial ischemia, coronary artery disease, coronary artery disorder[Ref]
Respiratory
Glimepiride-Rosiglitazone:
Common (1% to 10%): Nasopharyngitis
Rosiglitazone:
Common (1% to 10%): Upper respiratory infection
Postmarketing reports: Pulmonary edema, pleural effusions[Ref]
Nervous system
Glimepiride-Rosiglitazone:
Common (1% to 10%): Headache, dizziness
Glimepiride:
Common (1% to 10%): Headache, dizziness
Rosiglitazone:
Common (1% to 10%): Headache
Frequency not reported: Stroke[Ref]
General
The most commonly reported adverse reports included headache, hypoglycemia, and nasopharyngitis.[Ref]
Gastrointestinal
Glimepiride:
Common (1% to 10%): Nausea
Rare (less than 0.1%): Vomiting, gastrointestinal pain, diarrhea
Rosiglitazone:
Common (1% to 10%): Diarrhea[Ref]
Hepatic
Glimepiride:
Rare (less than 0.1%): Liver enzyme elevations,
Frequency not reported: Liver function impairment, e.g., cholestasis, jaundice, hepatitis, hepatic porphyria reactions and disulfiram-like reactions
Rosiglitazone:
Postmarketing reports: Hepatitis, hepatic enzyme elevations greater than 3 times the upper limit of normal, hepatic failure[Ref]
Hypersensitivity
Rosiglitazone:
Postmarketing reports: Anaphylactic reaction[Ref]
Dermatologic
Glimepiride:
Rare (less than 0.1%): Allergic skin reactions, e.g. pruritus, erythema, urticaria, and morbilliform or maculopapular eruptions
Frequency not reported: Porphyria cutanea tarda, photosensitivity reactions, allergic vasculitis
Rosiglitazone:
Postmarketing reports: Rash, pruritus, urticaria, angioedema, Stevens-Johnson syndrome[Ref]
Hematologic
Anemia was reported in 1.9% of patients receiving rosiglitazone as monotherapy. When taken in combination 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]
Glimepiride:
Frequency not reported: Leukopenia, agranulocytosis, thrombocytopenia, hemolytic anemia, aplastic anemia, pancytopenia
Rosiglitazone:
Common (1% to 10%): Anemia
Frequency not reported: Decrease in WBC counts[Ref]
Metabolic
The mechanism of weight gain is unclear, although it probably is due to a combination of fluid retention and fat accumulation. Dose-related weight gain was observed in trials with the combination glimepiride / rosiglitazone and rosiglitazone alone. Mean weight gain in patients receiving the combination glimepiride 4 mg/rosiglitazone 4 mg was 2.2 kg and 2.9 kg for patients receiving glimepiride 4 mg/rosiglitazone 8 mg.[Ref]
Glimepiride-Rosiglitazone:
Common (1% to 10%): Hypoglycemia
Frequency not reported: Weight gain
Glimepiride:
Common (1% to 10%): Hypoglycemia
Frequency not reported: Hyponatremia, syndrome of inappropriate antidiuretic hormone (SIADH) secretion, changes in serum lipids
Rosiglitazone:
Uncommon (0.1% to 1%): Hypoglycemia[Ref]
Ocular
Glimepiride:
Uncommon (0.1% to 1%): Blurred vision
Rosiglitazone:
Postmarketing reports: Diabetic macular edema with decreased visual acuity[Ref]
Musculoskeletal
Large long-term clinical trials have shown an increased incidence of bone fracture in patients receiving rosiglitazone in combination with sulfonylurea or metformin as rosiglitazone alone. This increased incidence appeared after the first year and persisted. The majority of fractures were observed in women and occurred in the upper arm, hand, and foot.[Ref]
Rosiglitazone:
Common: Back pain, arthralgia,
Frequency not reported: Fractures, bone mineral density decreases[Ref]
Other
Glimepiride:
Common (1% to 10%): Asthenia
Rosiglitazone:
Common (1% to 10%): Injury[Ref]
