Rosiglitazone and Gemfibrozil: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Gemfibrozil
Rosiglitazone
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
Increased rosiglitazone exposure
Interaction Deep Dive
Coadministration of rosiglitazone and a CYP2C8 inhibitor, such as gemfibrozil, increased the exposure of rosiglitazone by 127%2. Additionally, concomitant use of a thiazolidinedione (such as rosiglitazone) and a fibrate (such as gemfibrozil) may increase the risk of severe hypoglycemia, which may occur immediately or with a delayed-onset (after the first month of therapy) 1. If concomitant use is required, adjust diabetes treatment based on clinical response upon initiation or discontinuation of a CYP2C8 inhibitor. A decrease in the dose of rosiglitazone may be necessary 2.
Why it happens (mechanism)
Inhibition of CYP2C8-mediated metabolism of rosiglitazone
Literature reports
3 reports — tap to read
a) Concomitant use of rosiglitazone and gemfibrozil resulted in a significantly increased risk of severe hypoglycemia resulting in emergency department treatment or hospitalization during the first 30 days compared with pioglitazone and pravastatin (adjusted HR, 1.63; 95% CI, 1.21 to 2.19), as well as during the first 180 days (adjusted HR, 1.82; 95% CI, 1.5 to 2.2) in a propensity-score adjusted analysis (n=10,463). The increased risk of severe hypoglycemia with concomitant use peaked at 2.5-fold during days 30 to 59 and returned to null by day 180. The mechanism for this interaction may be more complex than CYP2C8 inhibition by fibrates, and may include a pharmacodynamic interaction involving the impact of fibrates on glucose. Patients received a thiazolidinedione (rosiglitazone or pioglitazone) and an antihyperlipidemic (atorvastatin, fenofibrate, fluvastatin, gemfibrozil, lovastatin, pravastatin, rosuvastatin, or simvastatin) during the study. Pravastatin served as the reference exposure as it is a negligible inhibitor of CYP450 isoenzymes and would not be expected to interact 1.
b) Concomitant administration of gemfibrozil (600 mg twice daily), an inhibitor of CYP2C8, and rosiglitazone (4 mg once daily) for 7 days increased rosiglitazone AUC by 127%, compared with the administration of rosiglitazone alone in a pharmacokinetic study 2.
c) A randomized crossover study with 2 phases demonstrated that gemfibrozil raised the mean rosiglitazone AUC 2.3-fold. Ten healthy volunteers were given gemfibrozil 600 mg or placebo twice daily for 4 days. On day 3, a single dose of rosiglitazone 4 mg was administered. Gemfibrozil considerably increased the plasma concentrations of rosiglitazone (C24 by about 10-fold). The AUC of rosiglitazone was significantly increased and the half-life prolonged by gemfibrozil (3.6 to 7.6 hours by gemfibrozil) 3.
Common questions
Can I take Rosiglitazone and Gemfibrozil together?
Increased rosiglitazone exposure Always confirm with your pharmacist or prescriber before making any change.
How serious is the Rosiglitazone and Gemfibrozil interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How strong is the evidence for this interaction?
The evidence is graded "established". Well documented — supported by controlled studies or strong clinical data.
Questions for your pharmacist
- Does my dose of Rosiglitazone or Gemfibrozil need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (3)
- Leonard CE, Han X, Bilker WB, et al: Comparative risk of severe hypoglycemia among concomitant users of thiazolidinedione antidiabetic agents and antihyperlipidemics. Diabetes Res Clin Pract 2016; 115:60-67. PubMed
- Product Information: AVANDIA(R) oral tablets, rosiglitazone maleate oral tablets. GlaxoSmithKline (per FDA), Research Triangle Park, NC, 2019. DailyMed
- Niemi M, Backman JT, Granfors M, et al: Gemfibrozil considerably increases the plasma concentrations of rosiglitazone. Diabetologia 2003; 46:1319-1323. PubMed
Keep reading about Gemfibrozil
Keep reading about Rosiglitazone
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist