Gemfibrozil with Rosiglitazone Interaction Details
Brand Names Associated with Gemfibrozil
- Gemfibrozil
- Lopid®
Brand Names Associated with Rosiglitazone
- Avandamet® (as a combination product containing Metformin, Rosiglitazone)
- Avandaryl® (as a combination product containing Glimepiride, Rosiglitazone)
- Avandia®
- Rosiglitazone
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 25, 2023
Interaction Effect
Increased rosiglitazone exposure
Interaction Summary
Coadministration of rosiglitazone and a CYP2C8 inhibitor, such as gemfibrozil, increased the exposure of rosiglitazone by 127%. 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) . 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 .
Severity
Major
Onset
Unspecified
Evidence
Established
How To Manage Interaction
Coadministration of rosiglitazone and a CYP2C8 inhibitor, such as gemfibrozil, may increase the exposure of rosiglitazone. 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) . 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 .
Mechanism Of Interaction
Inhibition of CYP2C8-mediated metabolism of rosiglitazone
Literature Reports
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 .
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 .
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) .
Gemfibrozil Overview
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Gemfibrozil is used with diet changes (restriction of cholesterol and fat intake) to reduce the amount of cholesterol and triglycerides (other fatty substances) in the blood in certain people with very high triglycerides who are at risk of pancreatic disease (conditions affecting the pancreas, a gland that produces fluid to break down food and hormones to control blood sugar). Gemfibrozil is also used in people with a combination of low high-density lipoprotein (HDL; 'good cholesterol') levels and high low-density lipoprotein (LDL; 'bad cholesterol') and triglyceride levels to reduce the risk of heart disease. Gemfibrozil is in a class of lipid-regulating medications called fibrates. It works by reducing the production of triglycerides in the liver.
Rosiglitazone Overview
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Rosiglitazone is used along with a diet and exercise program and sometimes with one or more other medications to treat type 2 diabetes (condition in which the body does not use insulin normally and therefore cannot control the amount of sugar in the blood). Rosiglitazone is in a class of medications called thiazolidinediones. It works by increasing the body's sensitivity to insulin, a natural substance that helps control blood sugar levels. Rosiglitazone is not used to treat type 1 diabetes (condition in which the body does not produce insulin and therefore cannot control the amount of sugar in the blood) or diabetic ketoacidosis (a serious condition that may occur if high blood sugar is not treated).
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Over time, people who have diabetes and high blood sugar can develop serious or life-threatening complications, including heart disease, stroke, kidney problems, nerve damage, and eye problems. Taking medication(s), making lifestyle changes (e.g., diet, exercise, quitting smoking), and regularly checking your blood sugar may help to manage your diabetes and improve your health. This therapy may also decrease your chances of having a heart attack, stroke, or other diabetes-related complications such as kidney failure, nerve damage (numb, cold legs or feet; decreased sexual ability in men and women), eye problems, including changes or loss of vision, or gum disease. Your doctor and other healthcare providers will talk to you about the best way to manage your diabetes.
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Definitions
Severity Categories
Contraindicated
These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.
Major
This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.
Moderate
This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.
Minor
While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.
Onset
Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.
Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.
Evidence
Level of documentation of the interaction.
Established: The interaction is documented and substantiated in peer-reviewed medical literature.
Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.
How To Manage The Interaction
Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.
It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.
Mechanism Of Interaction
The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.
Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.
Where Does Our Information Come From?
Information for our drug interactions is compiled from several drug compendia, including:
The prescribing information for each drug, as published on DailyMED, is also used.
Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.
The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.