Avandia

Name: Avandia

Brand names

  • Avandia®

What Is Avandia (Rosiglitazone)?

Avandia is the brand name of the prescription drug rosiglitazone, which is used along with diet and exercise to help people with type 2 diabetes control their blood-sugar levels.

If you have type 2 diabetes, your body doesn't make or use the hormone insulin normally, so it can't control the amount of sugar, or glucose, in the blood.

Avandia is in the thiazolidinedione class of drugs, which work by making your body's cells more sensitive to insulin.

The drug is manufactured by GlaxoSmithKline and was approved by the Food and Drug Administration (FDA) in 1999.

It's also available in a combination with metformin (Glucophage, Avandamet) and in a fixed-dose combination with glimepiride (Avandaryl).

In 2007, a review of research into rosiglitazone led to much controversy, investigations, lawsuits, and special FDA limits on prescribing the drug.

The review had indicated Avandia could cause heart attacks and death in some people.

But later, the FDA decided the risk of heart attack and death with Avandia was no different than it was for other diabetes drugs.

As of 2014, the FDA lifted some restrictions, but required providers who prescribe the drug to get special training about the research.

Avandia Warnings

Avandia used to have a black-box warning for heart attack and death, but the FDA has removed that warning.

Avandia still carries a black-box warning because it may cause or worsen congestive heart failure.

In congestive heart failure, your heart is unable to pump enough blood with oxygen to your body.

Before taking Avandia, tell your doctor about any conditions you've had that may be related to or affect the heart, such as:

  • Congestive heart failure
  • A heart attack, a heart defect, an irregular heartbeat, or other heart disease
  • Stroke or other blood-circulation conditions
  • High cholesterol
  • High blood pressure
  • Sleep apnea

Also tell your doctor if you have or have ever had:

  • A diabetic eye disease, such as macular edema
  • Liver disease

While taking Avandia, tell your doctor immediately or get emergency medical attention if you experience symptoms of congestive heart failure, which may include:

  • Shortness of breath
  • Difficulty walking or exercising
  • Swelling of the arms, hands, feet, ankles, or legs
  • Stomach swelling or pain
  • Waking during the night feeling short of breath
  • Frequent dry cough or wheezing
  • Fast or racing heartbeat
  • Difficulty thinking clearly
  • Confusion
  • Increased fatigue
  • Significant weight gain in a short period of time

Taking Avandia while you are using insulin may increase the risk of serious heart problems. Therefore, it's not recommended that you take Avandia if you are using insulin.

You should not take Avandia if you have type 1 diabetes (the body can't make insulin) or diabetic ketoacidosis (a dangerous condition that can occur if high blood sugar is untreated).

Women who take Avandia may be more likely to suffer from bone fractures in the upper arm, hand, or foot.

Avandia helps control type 2 diabetes but doesn't cure it. It may take two weeks for your blood-sugar level to decline and up to three months for its full effects.

Continue to take it even if you feel well. Don't stop taking it without talking to your doctor first.

Avandia may change your blood-sugar levels. You should know the symptoms of high (hyperglycemic) or low (hypoglycemic) blood-sugar episodes and be prepared to treat them.

Tell your physician if you experience an illness, fever, injury, or unusual stress while taking Avandia, because these can change your blood sugar and the Avandia dosage you need.

Your doctor will probably want to frequently check glucose levels while you're taking Avandia. Keep all healthcare appointments, including the ones for tests at a lab.

Always wear a diabetic identification (ID) bracelet to be sure you get proper treatment in case of an emergency.

Avandia Lawsuits

Lawsuits over Avandia have claimed that the drug's manufacturer did not inform people about potentially life-threatening risks, such as heart failure, heart attack, stroke, bone fractures, vision loss, or death.

As a result, GlaxoSmithKline has paid tens of millions of dollars in settlements.

But in 2013, an FDA review committee decided that Avandia and other rosiglitazone drugs do not cause more heart attacks or death than other diabetes medications, according to their review of research.

Pregnancy and Avandia

Avandia may cause harm to an unborn baby.

Tell your doctor if you're pregnant or plan to become pregnant before taking Avandia.

The drug may increase the chance that you'll become pregnant, even if you don't have regular monthly periods.

Talk to your doctor about effective birth-control methods.

You shouldn't breastfeed while taking Avandia, because it's not known whether the drug passes into breast milk or could harm a breastfeeding baby.

What is rosiglitazone, and how does it work (mechanism of action)?

Rosiglitazone is an oral drug that reduces the amount of sugar (glucose) in the blood. It is used for treating patients with type 2 diabetes and is in a class of anti-diabetic drugs called thiazolidinediones. The other member of this class is pioglitazone (Actos). Insulin is a hormone produced by the pancreas that is important for controlling the levels of glucose in the blood. Insulin stimulates the cells of the body to remove glucose from the blood and thereby lowers the level of glucose in the blood. Patients with type 2 diabetes cannot make enough insulin or are resistant to the effects of insulin (insulin resistance). As a result, the cells in their bodies do not remove enough glucose from the blood, and the level of glucose rises. Rosiglitazone often is referred to as an "insulin sensitizer" because it attaches to the insulin receptors on cells throughout the body and causes the cells to become more sensitive (more responsive) to insulin and remove more glucose from the blood. At least some insulin must be produced by the pancreas in order for rosiglitazone to work. Rosiglitazone was approved by the FDA in May 1999.

What brand names are available for rosiglitazone?

Avandia

Is rosiglitazone safe to take if I'm pregnant or breastfeeding?

There are no adequate studies of rosiglitazone in pregnant women. Rosiglitazone crosses the placenta and is detectable in fetal tissue.

It is unknown if rosiglitazone is secreted in breast milk. Therefore, the safety of rosiglitazone to nursing infants also is unknown.

What else should I know about rosiglitazone?

What preparations of rosiglitazone are available?

Tablets: 2, 4, and 8 mg.

How should I keep rosiglitazone stored?

Tablets should be kept at room temperature, 15 C -30 C (59 F -86 F).

Reviewed on 5/15/2017 References Medically reviewed by John P. Cunha, DO, FACOEP

REFERENCE:

FDA Prescribing Information for Avandia.

Adverse Effects

>10%

Increased LDL-cholesterol

Increased HDL-cholesterol

Increased total cholesterol

1-10%

Edema

Hypertension

Heart failure/congestive heart failure

Myocardial ischemia

Diarrhea

Upper respiratory tract infection

Frequency Not Defined

Accidental injury

Anemia

Back pain

Fatigue

Headache

Hypoglycemia

Myalgia

Sinusitis

Weight gain

Pharmacology

Mechanism of Action

Lowers glucose by improving target cell response to insulin without increasing pancreatic cell secretion; activates nuclear peroxisome proliferator-activated receptor gamma, which influences the production of gene products involved in glucose and lipid metabolism

Pharmacokinetics

Bioavailability: 99%

Onset of Action: Initial effect delayed; maximum effect may take up to 12 weeks

Peak Plasma Time: 1 hr

Protein Bound: >99%

Half-Life: 3-4 hr

Vd: 17.6 L

Metabolism: by hepatic CYP2C8 & CYP2C9 (minor extent)

Excretion: urine 64%; feces 22%

Avandia Overview

Avandia is a prescription medication used along with diet and exercise to treat type 2 diabetes. Avandia belongs to a group of drugs called thiazolidinediones. It can help your body respond better to insulin. 

This medication comes in tablet form and is taken 1 or 2 times a day, with or without food. 

Common side effects of Avandia include new or worse heart failure, headache, and cold-like symptoms.

Because Avandia has been associated with heart attack and stroke, it is available only through an access program. Both you and your doctor must be enrolled in the program. 

 

Avandia Drug Class

Avandia is part of the drug class:

  • Thiazolidinediones

Avandia Usage

  • Avandia comes as a tablet to be taken by mouth, with or without food.
  • It is usually taken once or twice daily. 
  • If you miss a dose of Avandia, take it as soon as you remember, unless it is time to take your next dose. Take your next dose at the usual time. Do not take double doses to make up for a missed dose.
  • Test your blood sugar regularly as your doctor tells you.
  • Your doctor should do blood tests to check your liver before you start Avandia and during treatment as needed. Your doctor should also do regular blood sugar tests (for example, “A1C”) to monitor your response to Avandia.

How should I take rosiglitazone?

Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not take this medicine in larger or smaller amounts or for longer than recommended.

You may take the medicine with or without food.

Your blood sugar will need to be checked often, and you may need other blood tests at your doctor's office.

Low blood sugar (hypoglycemia) can happen to everyone who has diabetes. Symptoms include headache, hunger, sweating, pale skin, irritability, dizziness, feeling shaky, or trouble concentrating. Always keep a source of sugar with you in case you have low blood sugar. Sugar sources include fruit juice, hard candy, crackers, raisins, and non-diet soda. Be sure your family and close friends know how to help you in an emergency.

If you have severe hypoglycemia and cannot eat or drink, use a glucagon injection. Your doctor can prescribe a glucagon emergency injection kit and tell you how to use it.

Check your blood sugar carefully during times of stress, travel, illness, surgery or medical emergency, vigorous exercise, or if you drink alcohol or skip meals. These things can affect your glucose levels and your dose needs may also change. Do not change your medication dose or schedule without your doctor's advice.

Use rosiglitazone regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely.

Rosiglitazone is only part of a treatment program that may also include diet, exercise, weight control, blood sugar testing, and special medical care. Follow your doctor's instructions very closely.

Store at room temperature away from moisture, heat, and light. Keep the bottle tightly closed when not in use.

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What should I avoid while taking rosiglitazone?

Avoid drinking alcohol. It can lower your blood sugar.

Cautions for Avandia

Contraindications

  • Initiation of therapy in patients with NYHA class III or IV CHF.1 110 118 128 157 (See Boxed Warning.)

  • History of hypersensitivity to the drug or any ingredient in the formulation.1

Warnings/Precautions

Warnings

Congestive Heart Failure

Risk of fluid retention; may cause or exacerbate CHF.1 116 117 128 141 143 Use of thiazolidinediones associated with approximately twofold increased risk of CHF.131 143 148 151 155 (See Boxed Warning and also see Edema under Cautions.)

Use with caution in patients with edema and in those who are at risk for CHF.1 110 117 148 Initiation of rosiglitazone not recommended in patients experiencing an acute coronary event.1 If an acute coronary event occurs, consider discontinuance of rosiglitazone during the acute phase.1 Use not recommended in patients with NYHA class III or IV cardiac status or those with symptomatic heart failure.1 110 113 118 149 150 Thiazolidinedione therapy should not be initiated in hospitalized patients with diabetes mellitus because of delayed onset of action and potential for increased vascular volume and CHF.114

Increased incidence of adverse cardiovascular events (e.g., edema, need for additional CHF therapy) reported in patients with NYHA class I or II heart failure receiving rosiglitazone in addition to other antidiabetic and CHF therapy.1 110 118 128 142 No change in left ventricular ejection fraction observed.1 110 118 128 142

Increased risk of CHF observed in patients receiving rosiglitazone and insulin compared with those receiving insulin alone.1 110 118 128 (See Specific Drugs under Interactions.)

General Precautions

Other Cardiovascular Effects

Findings from several meta-analyses of principally short-term trials and observational studies suggested a possible association between rosiglitazone and an increased risk of MI.1 110 118 128 130 132 144 148 151 155 217 220 However, these findings have not been confirmed in long-term (>3 years), prospective randomized studies.1 220 These studies, which include a cardiovascular outcomes trial (RECORD), generally have found no evidence of an increased risk of mortality or major adverse cardiovascular effects (MACE) with rosiglitazone compared with metformin and/or a sulfonylurea.1

Although some uncertainty remains regarding the cardiovascular risk of rosiglitazone, FDA states that concerns have been substantially reduced based on current evidence.220 223

Edema

Fluid retention reported; may lead to or exacerbate CHF.1 110 116 117 118 128 Weight gain reported; may involve fluid retention and fat accumulation.1 110 117 118

Use with caution in patients with edema and in those at risk for CHF.1 110 117 148 Monitor for weight gain and edema.1 117 Evaluate any patient developing edema within first few months of therapy for possible CHF.117 (See Congestive Heart Failure under Cautions.)

Musculoskeletal Effects

Risk of bone loss and fractures in women, and possibly men.1 110 118 125 126 127 139 145 147 151 Fractures reported more frequently in women receiving long-term therapy (4–6 years) with rosiglitazone (9.3%) than in women receiving metformin (5.1%) or glyburide (3.5%).1 110 118 125 126 147 Effects noted after first year of treatment and persisted throughout treatment.1 110 118 Majority of fractures were in upper limb (upper arm, hand, wrist) or distal lower limb (foot, ankle, fibula, tibia).1 110 118 125 127 147 Although increased risk of fracture may also apply to men, risk appears higher among women than men.1

Consider risk of fracture.1 110 118 125 127 147 Assess and maintain bone health according to current standards of care.1 110 125 147

Hematologic Effects

Possible dose-related decreases in hemoglobin (≤1 g/dL) and hematocrit (≤3.3%); usually evident within 3 months after initiation of therapy or dosage increase.1 30 110 Possible modest decreases in leukocyte counts.1 Hematologic effects may be related to plasma volume expansion.1 30

Ocular Effects

New-onset or worsening (diabetic) macular edema with decreased visual acuity reported; some patients reported concurrent peripheral edema.1 110 118 119 Some patients were symptomatic (e.g., blurred vision, decreased visual acuity); other cases were detected by routine ophthalmologic examination.1 110 118 Symptoms improved in some patients after discontinuance or rarely after dosage reduction.1 110 118 119

Regular eye examinations by an ophthalmologist recommended in patients with diabetes mellitus.1 110 114 118 Patients with any visual symptoms should be promptly evaluated by an ophthalmologist.1 110 118

Ovulatory Effects

Possible ovulation in premenopausal anovulatory women; risk of pregnancy unless contraceptive measures initiated.1 If unexpected menstrual dysfunction occurs, weigh risks versus benefits of continued therapy.1

Hepatic Effects

No evidence of hepatotoxicity in clinical studies to date.1 30 104 109 126 However, hepatitis, elevations in hepatic enzymes, and hepatic failure associated with fatalities reported during postmarketing experience.1

Monitor liver function tests prior to initiation of therapy and periodically thereafter according to clinician judgment.1 Do not initiate therapy if baseline ALT concentrations >2.5 times ULN.1 Evaluate patients with mildly elevated liver enzymes (e.g., ALT ≤2.5 ULN) prior to or during therapy to determine cause; initiate or continue drug with caution and close clinical monitoring.1 (See Hepatic Impairment under Cautions.)

Recheck liver enzymes as soon as possible if ALT increases to >3 times the ULN.1 Discontinue therapy if ALT remains elevated at >3 times ULN.1 Check liver function if manifestations suggestive of hepatic dysfunction (e.g., unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, dark urine) occur.1 Decision to continue therapy pending results of laboratory tests should be guided by clinician judgment.1 Discontinue if jaundice develops.1 110

Use of Fixed Combinations

When used in fixed combination with metformin hydrochloride or glimepiride, consider the cautions, precautions, and contraindications associated with the concomitant agent.110 118

Specific Populations

Pregnancy

Category C.1 110 Risk of birth defects, pregnancy loss, or other adverse outcomes increases in pregnancies complicated by hyperglycemia and may decrease with good glycemic control.1 110 118 Use during pregnancy only when potential benefits justify possible risk to the fetus.1 110 118 Most clinicians recommend use of insulin during pregnancy to maintain optimum control of blood glucose concentrations.1 110 118

Lactation

Distributed into milk in rats; not known whether distributed into human milk.1 110 118 146 Discontinue nursing or the drug.1 110 118 146

Pediatric Use

Rosiglitazone: Has been evaluated in children and adolescents 10–17 years of age.1 Manufacturer states that data are insufficient to recommend use in pediatric patients <18 years of age.1

Fixed combination with glimepiride: Safety and efficacy not established in pediatric patients <18 years of age.118 137

Fixed combination with metformin hydrochloride: Safety and efficacy not established in pediatric patients.110

ADA states that use of oral antidiabetic agents may be considered in children with type 2 diabetes mellitus because of the greater compliance and convenience and lack of evidence demonstrating better efficacy of insulin for type 2 diabetes mellitus.107

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults.1 (See Geriatric Patients under Dosage and Administration.)

Hepatic Impairment

Use with caution in patients with mild hepatic impairment (ALT ≤2.5 times the ULN).1 110 118 Use not recommended in patients with ALT >2.5 times ULN.1 110 118 (See Hepatic Effects under Cautions.)

Common Adverse Effects

Upper respiratory tract infection,1 30 injury,1 headache.1

Advice to Patients

  • Importance of patient reading medication guide before starting rosiglitazone and each time prescription is refilled.146

  • Importance of informing patients of the current state of knowledge regarding the cardiovascular risk of rosiglitazone, and that although there is some evidence suggesting an increased risk of MI compared with placebo, data from long-term clinical trials, including a cardiovascular outcomes trial, generally have not confirmed these findings.1

  • Importance of informing patients that rosiglitazone is not recommended for patients with symptomatic heart failure.1 146 149 150 Importance of identifying and reporting to a clinician potential symptoms of CHF (e.g., unusually rapid increase in weight, edema, unusual fatigue, shortness of breath).1 128 136 137 146

  • Importance of patients not taking rosiglitazone if they are allergic to the drug or any ingredients in the tablet.1 146 Signs and symptoms of severe allergic reaction include swelling of the face, lips, tongue, or throat; problems breathing or swallowing; rash, itching, or hives; blisters on the skin or in the mouth, nose, or eyes; skin peeling; faintness or dizziness; rapid heartbeat.1 146

  • Importance of taking exactly as prescribed.136 Importance of immediately contacting a clinician or a poison control center if accidental overdosage occurs.136 137

  • Importance of taking a missed dose as soon as possible, unless it is almost time for next dose.1 137 146 Do not double dose to make up for the missed dose.137 146

  • Importance of diet and exercise regimen adherence.1 110 136 137 146 Importance of regular monitoring of blood glucose and HbA1c.1 110 136 137 146

  • Importance of informing patients that rosiglitazone is not recommended in patients taking insulin due to potentially increased risk of CHF.1 146

  • Importance of continuing rosiglitazone therapy even if response is not evident in ≤2 weeks; full therapeutic response may not be evident for 2–3 months after initiation of therapy.1 136 137 146

  • Importance of regular eye examinations.1 110 118 136 137 Importance of reporting change in vision.1 146

  • Importance of liver function test monitoring and immediate reporting of potential manifestations of hepatotoxicity (e.g., nausea or vomiting, abdominal pain, unusual fatigue, loss of appetite, dark urine, yellowing of skin or whites of eyes).1 110 118 136 137

  • Risk of fractures (e.g., hand, upper arm, foot) in women.1 110 118 136 137 145 146 147

  • Risk of hypoglycemia in patients receiving concomitant antidiabetic agent therapy.1 Provide instructions regarding management of hypoglycemia, including recognition of symptoms, predisposing conditions, and treatment.1 136

  • Risk of pregnancy in premenopausal anovulatory women.1 110 137 Advise patients regarding use of effective contraception during therapy.1 110 118 136 137

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs (e.g., insulin and other drugs that affect glucose concentrations; antihypertensive agents; antilipemic agents; agents for heart failure, prevention of CHD, or stroke) and dietary or herbal supplements,137 as well as any concomitant illnesses (e.g., heart failure or other cardiac disease, type 1 diabetes mellitus, history of diabetic ketoacidosis, macular edema, liver disease, irregular menstrual periods).1 136 137 146

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.1 110 136 137 146

  • Importance of informing patients of other important precautionary information.1 110 118 (See Cautions.)

How is this medicine (Avandia) best taken?

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

  • Take with or without food.
  • To gain the most benefit, do not miss doses.
  • Keep taking Avandia as you have been told by your doctor or other health care provider, even if you feel well.

What do I do if I miss a dose?

  • Take a missed dose as soon as you think about it.
  • If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.

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 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.
  • Feeling very tired or weak.
  • Trouble swallowing.
  • A fast heartbeat.
  • Low blood sugar can happen. The chance of low blood sugar may be raised when this medicine is used with other drugs for high blood sugar (diabetes). Signs may be dizziness, headache, feeling sleepy, feeling weak, shaking, a fast heartbeat, confusion, hunger, or sweating. Call your doctor right away if you have any of these signs. Follow what you have been told to do if you get low blood sugar. This may include taking glucose tablets, liquid glucose, or some fruit juices.
  • This medicine 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.
  • Very bad and sometimes deadly liver problems have happened with Avandia. 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.

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

Common (1% to 10%): Back pain
Frequency not reported: Fractures[Ref]

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]

Gastrointestinal

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

Other

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

Some side effects of Avandia may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

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