Version July 2025
Thiazolidinediones, including rosiglitazone, cause or exacerbate congestive heart failure (CHF) in some patients. After initiation of rosiglitazone and after dose increases, observe patients carefully for signs and symptoms of heart failure (including excessive, rapid weight gain; dyspnea; and/or edema). If these signs and symptoms develop, manage the heart failure according to current standards of care. Furthermore, consider discontinuation or dose reduction of rosiglitazone.
Rosiglitazone is not recommended in patients with symptomatic heart failure. Initiation of rosiglitazone in patients with established New York Heart Association (NYHA) class III or IV heart failure is contraindicated.
A meta-analysis of 52 clinical trials (mean duration, 6 months; 16,995 total patients), most of which compared rosiglitazone with placebo, showed rosiglitazone to be associated with a statistically significant increased risk of myocardial infarction (MI). Three other trials (mean duration, 46 months; 14,067 total patients) comparing rosiglitazone with some other approved oral antidiabetic agents or placebo showed a statistically nonsignificant increased risk of MI and a statistically nonsignificant decreased risk of death. There have been no clinical trials directly comparing the cardiovascular risk of rosiglitazone and pioglitazone, another thiazolidinedione, but in a separate trial, pioglitazone (when compared with placebo) did not show an increased risk of MI or death.
Note: Avandia has been discontinued in the United States for >1 year.
Note: May require a dose reduction of insulin secretagogues (sulfonylureas, meglitinides) to avoid hypoglycemia; consider stopping insulin or reducing insulin dose (Ref).
Diabetes mellitus, type 2, treatment:
Note: May be used as an adjunctive agent or alternative monotherapy for select patients, including those in whom initial therapy with lifestyle intervention and metformin failed, or cannot take metformin, particularly when avoidance of hypoglycemia is desirable. Pioglitazone may have a more favorable cardiovascular profile compared to rosiglitazone; use of any thiazolidinedione has been associated with an increased risk of heart failure, and risk is increased with concomitant insulin use (Ref).
Oral: Initial: 4 mg/day as a single dose or in 2 divided doses If response is inadequate after 8 to 12 weeks of treatment, the dosage may be increased to 8 mg/day as a single dose or in 2 divided doses daily; maximum dose: 8 mg/day. Per some clinical trial data, 4 mg twice daily may lower fasting plasma glucose and HbA1c more effectively than 8 mg once daily.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
No dosage adjustment necessary.
Hepatic impairment prior to initiation: There are no dosage adjustments provided in the manufacturer's labeling. Clearance is significantly lower in hepatic impairment; therapy should not be initiated if the patient exhibits active liver disease or increased transaminases (ALT >2.5 times the upper limit of normal) at baseline.
Hepatic impairment during therapy: Discontinue therapy if ALT is persistently >3 times ULN or jaundice occurs.
Refer to adult dosing.
(For additional information see "Rosiglitazone (United States: Not available): Pediatric drug information")
Note: Avandia has been discontinued in the United States for >1 year.
Diabetes mellitus, type 2: Limited data available: Note: Rosiglitazone is not recommended for the management of type 2 diabetes mellitus (T2DM) in children and adolescents; if thiazolidinedione therapy is required, other agents are preferred (Ref).
Children ≥10 years and Adolescents: Oral: Initial: 2 mg twice daily; then increase to 4 mg twice daily after 8 weeks. Dosing presented was used in 233 pediatric patients as part of a larger multicenter comparative trial of treatments (n=699) in which rosiglitazone in combination with metformin was more effective than metformin alone or metformin and lifestyle changes at maintaining glycemic control (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Based on experience in adults, no dosage adjustment necessary.
Children ≥10 years and Adolescents:
Hepatic impairment prior to initiation: There are no dosage adjustments provided in the manufacturer's labeling. Clearance is significantly lower in hepatic impairment; based on recommendations in adults, therapy should not be initiated if the patient exhibits active liver disease or increased transaminases (ALT >2.5 times ULN) at baseline.
Hepatic impairment during therapy: Based on recommendations in adults, discontinue therapy if ALT is persistently >3 times ULN or jaundice occurs.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults administered monotherapy.
1% to 10%:
Cardiovascular: Edema (5%)
Hematologic & oncologic: Anemia (2%)
Nervous system: Headache (6%)
Respiratory: Upper respiratory tract infection (10%)
Frequency not defined:
Cardiovascular: Heart failure (including worsening heart failure), hypertension
Endocrine & metabolic: Dyslipidemia, hypoglycemia, weight gain
Gastrointestinal: Diarrhea
Neuromuscular & skeletal: Arthralgia, back pain, bone fracture (upper arm, hand, foot)
Respiratory: Nasopharyngitis
Postmarketing (any population):
Dermatologic: Pruritus, skin rash, Stevens-Johnson syndrome, urticaria
Endocrine & metabolic: Decreased HDL cholesterol (Gutschi 2006), SIADH (Berker 2008)
Hepatic: Hepatic failure (Su 2006), hepatitis (including cholestatic hepatitis, granulomatous hepatitis) (Dhawan 2002, Menees 2005), hepatotoxicity (Al-Salman 2000), increased liver enzymes, increased serum alkaline phosphatase (Hachey 2000)
Hypersensitivity: Anaphylaxis, angioedema
Neuromuscular & skeletal: Increased creatine phosphokinase in blood specimen (Kennie 2007)
Ophthalmic: Macular edema (Colucciello 2005)
Renal: Interstitial nephritis (Castledine 2006)
Respiratory: Pulmonary edema (Cekmen 2006)
US labeling: Hypersensitivity to rosiglitazone or any component of the formulation; NYHA Class III/IV heart failure (initiation of therapy)
Canadian labeling: Hypersensitivity to rosiglitazone or any component of the formulation; any stage of heart failure (eg, NYHA Class I, II, III, IV); serious hepatic impairment; pregnancy
Concerns related to adverse effects:
• Edema: Dose-related edema may occur. Use with caution in patients with edema; may increase plasma volume and/or cause fluid retention. Monitor for signs/symptoms of heart failure.
• Fractures: Increased incidence of bone fractures in females treated with rosiglitazone was observed during analysis of long-term trial; majority of fractures occurred in the upper arm, hand and foot (differing from the hip or spine fractures usually associated with postmenopausal osteoporosis). Consider risk of fracture prior to initiation and during use.
• Heart failure/cardiac effects: [US Boxed Warning]: Thiazolidinediones, including rosiglitazone, may cause or exacerbate congestive heart failure; closely monitor for signs and symptoms of congestive heart failure (eg, rapid weight gain, dyspnea, edema), particularly after initiation or dose increases. If heart failure develops, treat accordingly and consider dose reduction or discontinuation. Not recommended for use in any patient with symptomatic heart failure. Initiation of therapy is contraindicated in patients with NYHA class III or IV heart failure. A higher frequency of cardiovascular events has been noted in patients with NYHA class I or II heart failure treated with rosiglitazone. Use may also be associated with an increased risk of angina and MI. Use with caution in patients at risk for cardiovascular events and monitor closely. Discontinue if any deterioration in cardiac status occurs.
• Hematologic effects: May decrease hemoglobin, hematocrit, and/or WBC count (slight); effects may be related to increased plasma volume and/or dose-related. Changes in hemoglobin and hematocrit generally occurred during the first 3 months after initiation of therapy and after dose increases. Use with caution in patients with anemia.
• Hypoglycemia: The risk of hypoglycemia is increased when rosiglitazone is combined with other hypoglycemic agents; dosage adjustment of concomitant hypoglycemic agents may be necessary.
• Macular edema: Has been reported with thiazolidinedione use, including rosiglitazone; some patients with macular edema presented with blurred vision or decreased visual acuity, and most had peripheral edema at time of diagnosis. In addition to regular ophthalmic exams, diabetic patients with visual symptoms should receive prompt ophthalmic evaluation. Improvement in macular edema may occur with discontinuation of therapy.
• Weight gain: Dose-related weight gain observed with use; mechanism unknown but likely associated with fluid retention and fat accumulation.
Disease-related concerns:
• Bariatric surgery:
– Altered absorption: Absorption may be altered given the anatomic and transit changes created by gastric bypass and sleeve gastrectomy surgery (Mechanick 2020; Melissas 2013).
– Weight gain: Evaluate risk vs benefit and consider alternative therapy after gastric bypass, sleeve gastrectomy, and gastric banding; weight gain may occur (Apovian 2015).
• Hepatic impairment: Use with caution in patients with elevated transaminases (AST or ALT); do not initiate in patients with active liver disease or ALT >2.5 times the upper limit of normal (ULN) at baseline; evaluate patients with ALT ≤2.5 times ULN at baseline or during therapy for cause of enzyme elevation; during therapy, if ALT >3 times ULN, reevaluate levels promptly and discontinue if elevation persists or if jaundice occurs at any time during use.
• Ischemic heart disease: Do not initiate in patients with stable ischemic heart disease due to an increased risk of cardiovascular complications.
• Stress-related states: It may be necessary to discontinue therapy and administer insulin if the patient is exposed to stress (fever, trauma, infection, surgery).
Other warnings/precautions:
• Appropriate use: Not indicated for use in patients with type 1 diabetes mellitus or with diabetic ketoacidosis (DKA).
• Patient education: Diabetes self-management education (DSME) is essential to maximize the effectiveness of therapy.
Avandia has been discontinued in the United States for >1 year.
May be product dependent
Tablets (Avandia Oral)
2 mg (per each): $4.57
4 mg (per each): $6.78
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Generic: 2 mg, 4 mg, 8 mg
Health Canada requires written informed consent for new and current patients receiving rosiglitazone.
Oral: May be administered without regard to meals.
Oral: May be taken without regard to meals.
An FDA-approved patient medication guide, which is available with the product information and at http://www.fda.gov/downloads/Drugs/DrugSafety/ucm085922.pdf, must be dispensed with this medication.
Diabetes mellitus, type 2, treatment: Adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
Avandia [DSC] may be confused with Avalide, Coumadin
Avandia [US, Canada, and multiple international markets] may be confused with Avanza brand name for mirtazapine [Australia] and Prandin brand name for deflazacort [South Korea] and repaglinide [multiple international markets]
Substrate of CYP2C8 (Major), CYP2C9 (Minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Abiraterone Acetate: May increase hypoglycemic effects of Thiazolidinediones. Risk C: Monitor
Alpha-Lipoic Acid: May increase hypoglycemic effects of Antidiabetic Agents. Risk C: Monitor
Androgens: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor
Beta-Blockers (Beta1 Selective): May increase adverse/toxic effects of Antidiabetic Agents. Specifically, beta-blockers may mask the hypoglycemic symptoms of antidiabetic agents. Risk C: Monitor
Beta-Blockers (Nonselective): May increase hypoglycemic effects of Antidiabetic Agents. Beta-Blockers (Nonselective) may increase adverse/toxic effects of Antidiabetic Agents. Specifically, beta-blockers may mask the hypoglycemic symptoms of antidiabetic agents. Risk C: Monitor
Bortezomib: May increase therapeutic effects of Antidiabetic Agents. Bortezomib may decrease therapeutic effects of Antidiabetic Agents. Risk C: Monitor
Clarithromycin: May increase hypoglycemic effects of Thiazolidinediones. Risk C: Monitor
CYP2C8 Inducers (Moderate): May decrease serum concentration of Rosiglitazone. Risk C: Monitor
CYP2C8 Inhibitors (Strong): May increase serum concentration of Rosiglitazone. Risk C: Monitor
Direct Acting Antiviral Agents (HCV): May increase hypoglycemic effects of Antidiabetic Agents. Risk C: Monitor
Etilefrine: May decrease therapeutic effects of Antidiabetic Agents. Risk C: Monitor
Guanethidine: May increase hypoglycemic effects of Antidiabetic Agents. Risk C: Monitor
Hyperglycemia-Associated Agents: May decrease therapeutic effects of Antidiabetic Agents. Risk C: Monitor
Hypoglycemia-Associated Agents: Antidiabetic Agents may increase hypoglycemic effects of Hypoglycemia-Associated Agents. Risk C: Monitor
Inhibitors of the Proton Pump (PPIs and PCABs): May increase adverse/toxic effects of Thiazolidinediones. Specifically, the risk of osteoporosis or fracture may be increased. Risk C: Monitor
Insulin: May increase adverse/toxic effects of Rosiglitazone. Specifically, the risk of fluid retention, heart failure, and hypoglycemia may be increased with this combination. Risk X: Avoid
Letermovir: May increase serum concentration of Rosiglitazone. Risk C: Monitor
Lumacaftor and Ivacaftor: May decrease serum concentration of CYP2C8 Substrates (High Risk with Inhibitors or Inducers). Lumacaftor and Ivacaftor may increase serum concentration of CYP2C8 Substrates (High Risk with Inhibitors or Inducers). Risk C: Monitor
Maitake: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor
Monoamine Oxidase Inhibitors: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor
Pegvisomant: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor
Pregabalin: May increase fluid-retaining effects of Thiazolidinediones. Risk C: Monitor
Prothionamide: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor
Quinolones: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Quinolones may decrease therapeutic effects of Agents with Blood Glucose Lowering Effects. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Risk C: Monitor
Reproterol: May decrease therapeutic effects of Antidiabetic Agents. Risk C: Monitor
Ritodrine: May decrease therapeutic effects of Antidiabetic Agents. Risk C: Monitor
Salicylates: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor
Selective Serotonin Reuptake Inhibitor: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor
Sulfonylureas: Thiazolidinediones may increase hypoglycemic effects of Sulfonylureas. Management: Consider sulfonylurea dose adjustments in patients taking thiazolidinediones and monitor for hypoglycemia. Risk D: Consider Therapy Modification
Thiazide and Thiazide-Like Diuretics: May decrease therapeutic effects of Antidiabetic Agents. Risk C: Monitor
Vasodilators (Organic Nitrates): May increase adverse/toxic effects of Rosiglitazone. Specifically, a greater risk of ischemia and other adverse effects has been associated with this combination in some pooled analyses. Risk C: Monitor
Thiazolidinediones may cause ovulation in anovulatory premenopausal patients, increasing the risk of unintended pregnancy.
Thiazolidinediones are not recommended for patients with type 2 diabetes mellitus planning to become pregnant. Patients who could become pregnant should use effective contraception during therapy. Transition to a preferred therapy should be initiated prior to conception and contraception should be continued until glycemic control is achieved (ADA 2023; Alexopoulos 2019; Egan 2020)
Rosiglitazone crosses the placenta (Chan 2005).
Inadvertent use early in pregnancy has been reported, although in the majority of cases, the medication was stopped as soon as pregnancy was detected (Chan 2005; Kalyoncu 2005; Yaris 2004).
Poorly controlled diabetes during pregnancy can be associated with an increased risk of adverse maternal and fetal outcomes, including diabetic ketoacidosis, preeclampsia, spontaneous abortion, preterm delivery, delivery complications, major malformations, stillbirth, and macrosomia. To prevent adverse outcomes, prior to conception and throughout pregnancy, maternal blood glucose and HbA1c should be kept as close to target goals as possible but without causing significant hypoglycemia (ADA 2023).
Agents other than rosiglitazone are currently recommended to treat diabetes mellitus in pregnancy (ADA 2023).
It is not known if rosiglitazone is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother
Individualized medical nutrition therapy (MNT) based on American Diabetes Association recommendations is an integral part of therapy.
Fasting blood glucose.
HbA1c: Monitor at least twice yearly in patients who have stable glycemic control and are meeting treatment goals; monitor quarterly in patients in whom treatment goals have not been met, or with therapy change. Note: In patients prone to glycemic variability (eg, patients with insulin deficiency), or in patients whose HbA1c is discordant with serum glucose levels or symptoms, consider evaluating HbA1c in combination with blood glucose levels and/or a glucose management indicator (ADA 2023; KDIGO 2020).
Liver enzymes (prior to initiation of therapy, then periodically thereafter); evaluate patients with ALT ≤2.5 times ULN at baseline or during therapy for cause of enzyme elevation. Patients with an elevation in ALT >3 times ULN during therapy should be rechecked as soon as possible. If the ALT levels remain >3 times ULN, therapy with rosiglitazone should be discontinued.
Signs and symptoms of fluid retention or heart failure (periodically and with dose adjustments); weight gain (periodically and with dose adjustments); ophthalmic exams (at least every 1 to 2 years, or more frequently if symptoms dictate) (ADA 2023); fractures/fracture risk.
Recommendations for glycemic control in patients with diabetes:
Nonpregnant adults (AACE [Samson 2023]; ADA 2023):
HbA1c: <7% (a more aggressive [<6.5%] or less aggressive [<8%] HbA1c goal may be targeted based on patient-specific characteristics). Note: In patients using a continuous glucose monitoring system, a goal of time in range >70% with time below range <4% is recommended and is similar to a goal HbA1c <7%.
Preprandial capillary blood glucose: 80 to 130 mg/dL (SI: 4.4 to 7.2 mmol/L) (more or less stringent goals may be appropriate based on patient-specific characteristics).
Peak postprandial capillary blood glucose (~1 to 2 hours after a meal): <180 mg/dL (SI: <10 mmol/L) (more or less stringent goals may be appropriate based on patient-specific characteristics).
Older adults (≥65 years of age) (ADA 2023):
Note: Consider less strict targets in patients who are using insulin and/or insulin secretagogues (sulfonylureas, meglitinides) (ES [LeRoith 2019]).
HbA1c: <7% to 7.5% (healthy); <8% (complex/intermediate health). Note: Individualization may be appropriate based on patient and caregiver preferences and/or presence of cognitive impairment. In patients with very complex or poor health (ie, limited remaining life expectancy), consider making therapy decisions based on avoidance of hypoglycemia and symptomatic hyperglycemia rather than HbA1c level.
Preprandial capillary blood glucose: 80 to 130 mg/dL (SI: 4.4 to 7.2 mmol/L) (healthy); 90 to 150 mg/dL (SI: 5 to 8.3 mmol/L) (complex/intermediate health); 100 to 180 mg/dL (SI: 5.6 to 10 mmol/L) (very complex/poor health).
Bedtime capillary blood glucose: 80 to 180 mg/dL (SI: 4.4 to 10 mmol/L) (healthy); 100 to 180 mg/dL (SI: 5.6 to 10 mmol/L) (complex/intermediate health); 110 to 200 mg/dL (SI: 6.1 to 11.1 mmol/L) (very complex/poor health).
Classification of hypoglycemia (ADA 2023):
Level 1: 54 to 70 mg/dL (SI: 3 to 3.9 mmol/L); hypoglycemia alert value; initiate fast-acting carbohydrate (eg, glucose) treatment.
Level 2: <54 mg/dL (SI: <3 mmol/L); threshold for neuroglycopenic symptoms; requires immediate action.
Level 3: Hypoglycemia associated with a severe event characterized by altered mental and/or physical status requiring assistance.
Thiazolidinedione antidiabetic agent that lowers blood glucose by improving target cell response to insulin, without increasing pancreatic insulin secretion. It has a mechanism of action that is dependent on the presence of insulin for activity. Rosiglitazone is an agonist for peroxisome proliferator-activated receptor-gamma (PPARgamma). Activation of nuclear PPARgamma receptors influences the production of a number of gene products involved in glucose and lipid metabolism. PPARgamma is abundant in the cells within the renal collecting tubules; fluid retention results from stimulation by thiazolidinediones which increases sodium reabsorption.
Onset of action: Delayed; Maximum effect: Up to 12 weeks
Distribution: Vdss (apparent): 17.6 L
Protein binding: 99.8%; primarily albumin
Metabolism: Hepatic (99%) via CYP2C8; minor metabolism via CYP2C9
Bioavailability: 99%
Half-life elimination: 3 to 4 hours; prolonged by approximately 2 hours in patients with moderate-to-severe hepatic impairment
Time to peak, plasma: 1 hour; delayed with food
Excretion: Urine (~64%) and feces (~23%) as metabolites
Hepatic function impairment: In moderate to severe liver disease (Child-Pugh class B or C), unbound oral Cl was significantly lower, Cmax and AUC were increased 2- and 3-fold, respectively.
Sex: Mean oral Cl in women was approximately 6% lower.
Body weight: Cl and steady-state Vd increase with increased body weight.
