II. Background
- Listed for historical purposes only
- Discontinued in the U.S. in 2011
III. Indications
-
Pioglitazone is preferred instead of Rosiglitazone
- Vascular disease risk increase with Rosiglitazone (see adverse effects below)
- Rosiglitazone was discontinued in the U.S. in 2011
-
Oral Hypoglycemic for Type II Diabetes Mellitus
- Second line agent (although falling out of favor in 2012 due to risks)
- Add to other Oral Hypoglycemic agents
- Diabetes with coronary Vasospastic Angina pectoris
- Insulin Resistance Syndromes (experimental)
-
Psoriasis (experimental)
- Thiazolidinediones activate PPARs
- Peroxisome proliferator-activated receptors (PPARs)
- PPARs have antiinflammatory activity in Psoriasis
- Thiazolidinediones activate PPARs
IV. Contraindications
- Type 1 Diabetes Mellitus
- Liver disease (ALT > 2.5x upper limit of normal)
- CHF NYA Class III or Class IV Heart Failure
- Osteoporosis or Osteopenia
- Bladder Cancer
V. Precautions
- CHF exacerbation risk (and contraindicated for NYHA Class III or IV) for ALL Glitazones (FDA Black Box warning)
- Rosiglitazone is now limited use due to increased Cardiovascular Risk
- FDA has restricted further Rosiglitazone use to those with refractory Type II Diabetes on other agents
- FDA will loosen restrictions in 2014 based on re-analysis of RECORD Study data, but caution is still advised
- (2014) Presc Lett 21(1): 3
VI. Mechanism
- Thiazolidinedione derivative
- Primary mechanism: Increases peripheral tissue Insulin sensitivity
- Secondary mechanism: Decreases hepatic Glucose production
- Acts at liver, skeletal Muscle and fat cells
- Activates peroxisome proliferator activated receptors
- Receptors known as PPARS
- Reduces Insulin Resistance
- May independently reduce Cardiovascular Risk
- Increases Glucose uptake
- Decreases hepatic Glucose output
- Shifts fat deposition from visceral to subcutaneous
- Decreases free Fatty Acid levels
VII. Medications
- Rosiglitazone (Avandia) tablets: 2 mg, 4 mg
VIII. Dosing
- Use Rosiglitazone only with caution (Pioglitazone is preferred instead)
- Conversion to Pioglitazone
- Rosiglitazone 2 mg is equivalent to Pioglitazone 15 mg
- Rosiglitazone 4 mg is equivalent to Pioglitazone 30 mg
- Rosiglitazone 8 mg is equivalent to Pioglitazone 45 mg
- Rosiglitazone (Avandia)
- Initial: 4 mg PO qd (or 2 mg PO bid)
- Maximum: 8 mg per day (4 mg if on Insulin)
IX. Adverse Effects
- Hepatotoxicity and Liver Failure
- Associated with Troglitazone use
- Troglitazone removed from U.S. market in March 2000
- Rosiglitazone and Pioglitazone may also cause this
- Follow Liver Function Tests closely
- Especially follow in first year
- References
- Fluid retention
- Congestive Heart Failure risk (see below)
- Peripheral Edema (in 3-5% of patients)
- Moderate weight gain (1-3 kg)
- Mild Anemia
- Variable lipid effects
- Pioglitazone (Actos)
- Lowers Triglycerides by 9-12%
- Raises HDL Cholesterol by 12-19%
- Rosiglitazone (Avandia):
- RAISES Triglycerides by 15%
- Raises HDL Cholesterol by 8-19%
- Raises LDL Cholesterol
- References
- (2005) Prescriber's Letter 12(8):43
- Pioglitazone (Actos)
- Risks of adverse effects (compounded when combined with Insulin)
- Weight gain (3-4 kg)
- Edema (8-10% of cases)
- Congestive Heart Failure
- Observe patients with CHF risk closely
- Hypoglycemia risk
-
Fracture Risk and Decreased Bone Density (Osteoporosis risk)
- Class effect
- Odds Ratio approaches 2.5 for Glitazone use >8 months
- (2008) Arch Intern Med 168:820-5 [PubMed]
-
Cardiovascular Risk
- Rosiglitazone (Avandia) appears to increase CAD risk
- No longer recommended as a first-line agent
-
Pioglitazone (Actos) may slightly decrease CAD risk
- Atherosclerosis may be slowed by Actos
- Nissen (2008) JAMA 299(13):1561-73 [PubMed]
- Rosiglitazone (Avandia) appears to increase CAD risk
-
Bladder Cancer risk
- Risk of up to 11 per 10,000 cases per patients taking Pioglitazone (actos) >1 year
- Mamtani (2012) J Natl Cancer Inst 104 (18): 1411-1421 [PubMed]
X. Safety
- Pregnancy Category C
- Avoid in Lactation
XI. Pharmacokinetics
- Hepatic metabolism by Cytochrome P450: CYP2C8
XII. Monitoring
-
Liver Function Tests
- Initial: Baseline and in 6-12 weeks
- Later: Every 6 months
- Do not start medication if LFTs > 2.5x normal
- Stop medication if LFTs >3x normal
- Follow weight for weight gain (esp. if CHF risk)
XIII. Efficacy
- Lowers Hemoglobin A1C 0.5 to 1.5%
- Delays Insulin need when added to Metformin, Sulfonylureas
XIV. Resources
- Rosiglitazone (DailyMed)
Images: Related links to external sites (from Bing)
Related Studies
Definition (NCI_NCI-GLOSS) | The active ingredient in a drug that helps control the amount of glucose (sugar) in the blood and is being studied in the prevention and treatment of some types of cancer. Rosiglitazone stops cells from growing and may prevent the growth of new blood vessels that tumors need to grow. It is a type of thiazolidinedione and a type of antiangiogenesis agent. |
Definition (NCI) | An agent belonging to the glitazone class of antidiabetic agents with antihyperglycemic and anti-inflammatory activities. In addition to its selective affinity for peroxisome proliferator-activated receptor (PPAR) gamma and its ability to lower blood glucose levels, rosiglitazone also exerts anti-inflammatory activity through its ability to inhibit nuclear factor-kappaB (NF-KB) activity and increase I-kappaB levels. In addition, rosiglitazone may cause fluid retention and may worsen congestive heart failure. This agent is also associated with an increased risk of heart attacks. |
Definition (CSP) | peroxisome proliferator activated receptor agonist; reduces lipid availability; improves insulin action and glucoregulation. |
Definition (PDQ) | An orally-active thiazolidinedione with antidiabetic properties and potential antineoplastic activity. Rosiglitazone activates peroxisome proliferator-activated receptor gamma (PPAR-gamma), a ligand-activated transcription factor, thereby inducing cell differentiation and inhibiting cell growth and angiogenesis. This agent also modulates the transcription of insulin-responsive genes, inhibits macrophage and monocyte activation, and stimulates adipocyte differentiation. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=37793&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=37793&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C2583" NCI Thesaurus) |
Concepts | Pharmacologic Substance (T121) , Organic Chemical (T109) |
MSH | C089730 |
SnomedCT | 326053005, 395869000 |
LNC | LP171637-4 |
English | 5-((4-(2-methyl-2-(pyridinylamino)ethoxy)phenyl)methyl)-2,4-thiazolidinedione-2-butenedioate, rosiglitazone, rosiglitazone [Chemical/Ingredient], 2,4-Thiazolidinedione, 5-004-02-((((methyl-2-pyridinylamino)ethoxy)phenyl)methyl)-, ROSIGLITAZONE, Rosiglitazone (product), Rosiglitazone (substance), Rosiglitazone, ROS |
Spanish | rosiglitazona (producto), rosiglitazona (sustancia), rosiglitazona |
Ontology: Avandia (C0875967)
Concepts | Pharmacologic Substance (T121) , Organic Chemical (T109) |
MSH | C089730 |
English | Avandia, rosiglitazone maleate (Avandia), avandia, Glaxo Wellcome brand of rosiglitazone maleate, GlaxoSmithKline brand of rosiglitazone maleate, SmithKline Beecham brand of rosiglitazone maleate |