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Glimepiride / rosiglitazone Side Effects

For the Consumer

Applies to glimepiride/rosiglitazone: oral tablet

Warning

  • This drug may cause or make heart failure worse in some people. Tell your doctor if you have ever had heart failure. Do not take this drug if you have moderate to very bad heart failure or if you have any signs of heart failure. You will be watched closely for signs of heart failure when you start this drug and if your dose is raised. Call your doctor right away if you have swelling in the arms or legs, shortness of breath or trouble breathing, sudden weight gain or weight gain that is not normal, or are feeling very tired. Talk with your doctor.

What are some side effects that I need to call my doctor about right away?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Weakness on 1 side of the body, trouble speaking or thinking, change in balance, drooping on one side of the face, or blurred eyesight.
  • Bone pain.
  • Change in eyesight.
  • A fast heartbeat.
  • A heartbeat that does not feel normal.
  • Feeling very tired or weak.
  • Very bad dizziness or passing out.
  • Period (menstrual) changes.
  • Low blood sugar may occur. Signs may be dizziness, headache, feeling sleepy, feeling weak, shaking, a fast heartbeat, confusion, hunger, or sweating. Call the doctor right away if any of these signs occur. Follow what you have been told to do if low blood sugar occurs. This may include taking glucose tablets, liquid glucose, or some fruit juices.
  • A very bad skin reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis) may happen. It can cause very bad health problems that may not go away, and sometimes death. Get medical help right away if you have signs like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in your mouth, throat, nose, or eyes.
  • Very bad and sometimes deadly liver problems have happened with this drug. Call your doctor right away if you have signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
  • This drug may raise the chance of heart attack. Call your doctor right away if you have chest pain or pressure; pain in the arms, back, neck, jaw, or stomach; shortness of breath; cold sweats; very bad dizziness or passing out; or very upset stomach or throwing up.

What are some other side effects of this drug?

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

For Healthcare Professionals

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

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]

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]

Ocular

Glimepiride:

Uncommon (0.1% to 1%): Blurred vision

Rosiglitazone:

Postmarketing reports: Diabetic macular edema with decreased visual acuity[Ref]

Musculoskeletal

Rosiglitazone:

Common: Back pain, arthralgia,

Frequency not reported: Fractures, bone mineral density decreases[Ref]

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]

Other

Glimepiride:

Common (1% to 10%): Asthenia

Rosiglitazone:

Common (1% to 10%): Injury[Ref]

References

1. "Product Information. Avandaryl (glimepiride-rosiglitazone)." GlaxoSmithKline, Research Triangle Park, NC.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Some side effects may not be reported. You may report them to the FDA.

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