Metformin / rosiglitazone Side Effects

Not all side effects for metformin / rosiglitazone may be reported. You should always consult a doctor or healthcare professional for medical advice. Side effects can be reported to the FDA here.

For the Consumer

Applies to metformin / rosiglitazone: oral tablet

In addition to its needed effects, some unwanted effects may be caused by metformin / rosiglitazone. In the event that any of these side effects do occur, they may require medical attention.

You should check with your doctor immediately if any of these side effects occur when taking metformin / rosiglitazone:

More common
  • Pale skin
  • troubled breathing with exertion
  • unusual bleeding or bruising
  • unusual tiredness or weakness
Less common
  • Anxiety
  • blurred vision
  • chest pain or discomfort
  • chills
  • cold sweats
  • coma
  • confusion
  • cool, pale skin
  • depression
  • dilated neck veins
  • dizziness
  • extreme fatigue
  • fast heartbeat
  • headache
  • increased hunger
  • irregular breathing
  • irregular heartbeat
  • nausea
  • nightmares
  • seizures
  • shakiness
  • slurred speech
  • swelling of the face, fingers, feet, or lower legs
  • weight gain
Rare
  • Abdominal or stomach discomfort
  • decreased appetite
  • diarrhea
  • fast, shallow breathing
  • general feeling of discomfort
  • muscle pain or cramping
  • sleepiness
Incidence not known
  • Change in vision
  • dark urine
  • decreased urine output
  • hives or welts, itching, or skin rash
  • large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
  • pain or discomfort in the arms, jaw, back, or neck
  • redness of the skin
  • stomach pain
  • sweating
  • vomiting

Some of the side effects that can occur with metformin / rosiglitazone may not need medical attention. As your body adjusts to the medicine during treatment these side effects may go away. Your health care professional may also be able to tell you about ways to reduce or prevent some of these side effects. If any of the following side effects continue, are bothersome or if you have any questions about them, check with your health care professional:

More common
  • Body aches or pain
  • cough, fever, sneezing, or sore throat
  • difficulty with breathing
  • ear congestion
  • loss of voice
  • pain or tenderness around the eyes and cheekbones
  • stuffy or runny nose
Less common
  • Back pain
  • cold or flu-like symptoms
  • difficulty with moving
  • pain in the joints

For Healthcare Professionals

Applies to metformin / rosiglitazone: oral tablet

General

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

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

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.

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 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.

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

Hematologic

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.

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

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.

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

Hypersensitivity

Rosiglitazone:
Postmarketing reports: Anaphylactic reaction, urticaria, angioedema

Ocular

Rosiglitazone:
Postmarketing reports: Diabetic macular edema with decreased visual acuity

Musculoskeletal

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.

Very common: (10% or more): Arthralgia (10.6%)
Common (1% to 10%): Back pain, arthritis
Frequency not reported: Fractures

Dermatologic

Metformin:
Very rare (less than 0.01%): Mild erythema

Rosiglitazone:
Postmarketing reports: Rash, pruritus, urticaria, angioedema, Stevens-Johnson syndrome

Endocrine

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

Genitourinary

Common (1% to 10%): Urinary tract infection

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

Immunologic

Common (1% to 10%): Viral infection

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

Other

Very common (10% or more): Injury (16.9%)
Common (1% to 10%): Fatigue, pain

Disclaimer: Every effort has been made to ensure that the information provided is accurate, up-to-date and complete, but no guarantee is made to that effect. In addition, the drug information contained herein may be time sensitive and should not be utilized as a reference resource beyond the date hereof. This material does not endorse drugs, diagnose patients, or recommend therapy. This information is a reference resource designed as supplement to, and not a substitute for, the expertise, skill , knowledge, and judgement of healthcare practitioners in patient care. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate safety, effectiveness, or appropriateness for any given patient. Drugs.com does not assume any responsibility for any aspect of healthcare administered with the aid of materials provided. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the substances you are taking, check with your doctor, nurse, or pharmacist.

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