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Avandamet Side Effects

Generic name: metformin / rosiglitazone

Medically reviewed by Drugs.com. Last updated on Oct 9, 2023.

Note: This document contains side effect information about metformin / rosiglitazone. Some dosage forms listed on this page may not apply to the brand name Avandamet.

Applies to metformin / rosiglitazone: oral tablet.

Warning

Oral route (Tablet)

Thiazolidinediones may cause or worsen congestive heart failure in some patients, Use in patients with established NYHA class III or IV heart failure is contraindicated and use in patients with symptomatic heart failure is not recommended. Monitor patients for signs and symptoms of heart failure after initiation or dose increases. If heart failure occurs, consider reducing the dose or discontinuing rosiglitazone therapy and manage patient according to current standards of care. Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metformin-associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms. The risk of lactic acidosis is increased with renal impairment, concomitant use of certain drugs (eg, carbonic anhydrase inhibitors, such as topiramate), age 65 years old or greater, having a radiologic study with contrast, surgery and other procedures, hypoxic states (eg, acute congestive heart failure), excessive alcohol intake, and hepatic impairment. If lactic acidosis is suspected, immediately discontinue use and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended.

Serious side effects of Avandamet

Along with its needed effects, metformin / rosiglitazone may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking metformin / rosiglitazone:

More common

Less common

Rare

Incidence not known

Other side effects of Avandamet

Some side effects of metformin / rosiglitazone may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

Less common

For Healthcare Professionals

Applies to metformin / rosiglitazone: oral tablet.

General

The most commonly reported adverse reports included upper respiratory tract infections, injury, and headache.[Ref]

Metabolic

Metformin-Rosiglitazone:

Very common (10% or more): Hypoglycemia (12%)

Common (1% to 10%): Hypercholesterolemia, hyperlipidemia

Uncommon (0.1% to 1%): Weight gain

Rosiglitazone:

Common (1% to 10%): Hypoglycemia (8%), hypercholesterolemia

Uncommon (0.1% to 1%): Weight gain

Frequency not reported: Increases in waist and hip circumference

Metformin:

Common (1% to 10%): Hypoglycemia (9%)

Very rare (less than 0.01%): Lactic acidosis[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, the median weight change with rosiglitazone at 4 years was plus 3.5 kg; with metformin it was a weight loss of 2.4 kg. In drug-naive patients, no overall change in median weight was observed in clinical trials.[Ref]

Cardiovascular

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]

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 CHF (secondary endpoint). In this trial, 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 has been reported in rosiglitazone clinical trials. Healthy volunteers receiving rosiglitazone 8 mg once daily for 8 weeks experienced a statistically significant increase in median plasma volume compared with placebo.

-Among patients with inadequate glycemic control on diet and exercise (n=468), edema was reported in 6% of patients starting on combination rosiglitazone/metformin, 7% starting on rosiglitazone alone, and 3% on metformin alone.

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]

Hematologic

Metformin-Rosiglitazone:

Very common (10% or more): Anemia (up to 16.7%)

Metformin:

Common (1% to 10%): Anemia

Very rare (less than 0.01%): Subnormal vitamin B12 levels

Rosiglitazone:

Common (1% to 10%): Anemia

Frequency not reported: Decrease in WBC counts[Ref]

Among patients inadequately controlled on rosiglitazone monotherapy switched to rosiglitazone/metformin combination treatment, anemia was reported in 7.1% (n=338) of patients compared with 1.9% (n=2526) and 2.2% (n=225) of patient receiving rosiglitazone or metformin monotherapy. Lower pretreatment hemoglobin/hematocrit levels in patients receiving combination therapy may have contributed to the higher reporting rate. Laboratory findings have shown dose-related decreases in hemoglobin and hematocrit in patients receiving rosiglitazone; mean decreases of 1 g/dL and up to 3.3% were seen in hemoglobin and hematocrit, respectively. These changes primarily occurred during the first 3 months or following a dose increase. They may be related to increased plasma volume.[Ref]

Gastrointestinal

Very common (10% or more): Nausea/vomiting (16%), diarrhea (14%)

Common (1% to 10%): Dyspepsia, abdominal pain, loose stools, constipation, flatulence, gastritis

Uncommon (0.1% to 1%): Anorexia

side effects have included nausea, anorexia, metallic taste, diarrhea, dyspepsia, flatulence, and abdominal pain. Diarrhea has been reported by 12.7% of patients in clinical trials.[Ref]

Respiratory

Very common (10% or more): Upper respiratory tract infection (16% to 28%)

Common (1% to 10%): Nasopharyngitis, sinusitis, bronchitis, coughing, pharyngitis

Rosiglitazone:

Frequency not reported: Dyspnea

Postmarketing reports: Pulmonary edema, pleural effusions[Ref]

Hypersensitivity

Rosiglitazone:

Postmarketing reports: Anaphylactic reaction, urticaria, angioedema[Ref]

Ocular

Rosiglitazone:

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

Musculoskeletal

Very common: (10% or more): Arthralgia (10.6%)

Common (1% to 10%): Back pain, arthritis

Frequency not reported: Fractures[Ref]

Large long-term rosiglitazone clinical trials have shown an increased incidence of bone fracture in patients receiving rosiglitazone both alone and in combination with sulfonylureas or metformin. 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]

Dermatologic

Metformin:

Very rare (less than 0.01%): Mild erythema

Rosiglitazone:

Postmarketing reports: Rash, pruritus, urticaria, angioedema, Stevens-Johnson syndrome[Ref]

Endocrine

Frequency not reported: Resumption of ovulation in premenopausal, anovulatory women, hormonal imbalance[Ref]

Genitourinary

Common (1% to 10%): Urinary tract infection[Ref]

Hepatic

Rosiglitazone:

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]

Immunologic

Common (1% to 10%): Viral infection[Ref]

Nervous system

Very common (10% or more): Headaches (11%)

Common (1% to 10%): Dizziness

Metformin:

Common (1% to 10%): Metallic taste

Rosiglitazone:

Frequency not reported: Stroke[Ref]

Other

Very common (10% or more): Injury (16.9%)

Common (1% to 10%): Fatigue, pain[Ref]

References

1. Product Information. Avandamet (metformin-rosiglitazone). GlaxoSmithKline. 2002.

2. Cerner Multum, Inc. UK Summary of Product Characteristics.

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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