BLACK BOX WARNING
- may cause or exacerbate congestive heart failure; risk of myocardial ischemia; not recommended when less risky alternatives exist
rosiglitazone
Brand: Avandia
⚠ BBW Prototype: pioglitazone
Drug Class: thiazolidinedione
Drug Family: antidiabetic
Subclass: PPAR-gamma agonist
Organ Systems: endocrine
Mechanism of Action
Activates nuclear PPAR-gamma receptors to improve insulin sensitivity in peripheral tissues; similar mechanism to pioglitazone. Previously widely used but substantially restricted due to meta-analysis data suggesting increased myocardial infarction risk.
PPAR-gamma receptor
Indications
- type 2 diabetes mellitus (restricted use — only for patients who cannot use other agents and are already on rosiglitazone)
Contraindications
- NYHA Class III–IV heart failure
- established ischemic heart disease
- any other situation where pioglitazone is available and preferred
Adverse Effects
Common
- weight gain
- edema
- upper respiratory infections
Serious
- myocardial infarction risk (controversial but basis for restriction)
- heart failure exacerbation
- bladder cancer (less than pioglitazone)
- bone fractures (females)
Pharmacokinetics (ADME)
| Absorption | oral bioavailability ~99% |
| Distribution | 99.8% protein bound |
| Metabolism | hepatic via CYP2C8 (major) |
| Excretion | renal (64%) and fecal (23%) |
| Half-life | 3–4 hours |
| Onset | days to weeks |
| Peak | 1 hour |
| Duration | ongoing |
| Protein Binding | 99.8% |
| Vd | 17.6 L |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| gemfibrozil | CYP2C8 inhibition increases rosiglitazone 2-fold | major |
Nursing Considerations
- Understand that rosiglitazone use is now restricted and requires REMS program enrollment in the US due to MI risk concerns.
- Monitor for heart failure signs (weight gain, edema, dyspnea); hold and consult prescriber immediately.
- Monitor LFTs periodically; hepatotoxicity risk similar to pioglitazone.
- Counsel patients about non-cardiac risks: fractures in women, and weight gain.
Clinical Pearls
- The FDA imposed significant restrictions on rosiglitazone in 2010 following meta-analyses suggesting increased MI risk; these restrictions were partially lifted in 2013 after a more thorough evaluation.
- Pioglitazone is now strongly preferred over rosiglitazone because pioglitazone's cardiovascular data (PROactive trial) suggest benefit rather than harm.
Safety Profile
Pregnancy avoid
Lactation avoid
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.