Fenofibrate with Rosiglitazone Interaction Details

Brand Names Associated with Fenofibrate

Brand Names Associated with Rosiglitazone

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 15, 2023

Interaction Effect

A paradoxical decrease in HDL-C

Interaction Summary

Concomitant use of fenofibrate and rosiglitazone may cause a paradoxical decrease in HDL-C levels, resulting in the increased risk for the development of atherosclerosis. Use with caution  or consider alternative medications should a decrease in HDL-C occur . Consider monitoring cholesterol levels closely, specifically, routine monitoring of HDL-C levels .

Severity

Moderate

Onset

Delayed

Evidence

Established

How To Manage Interaction

Concomitant use of fenofibrate and rosiglitazone may cause an unexpected decrease in HDL-C levels in a minority of patients, resulting in an increased risk for the development of atherosclerosis. Use with caution  or consider alternative medications should a decrease in HDL-C occur . Consider monitoring cholesterol levels closely, specifically, routine monitoring of HDL-C levels with concomitant administration of these drugs .

Mechanism Of Interaction

Multiple mechanisms, possibly involving HDL-C metabolism

Literature Reports

A) A prospective study of 2 patients receiving concomitant fenofibrate and rosiglitazone for the treatment of type 2 diabetes mellitus demonstrated a high probability of a drug interaction that resulted in significant reductions in HDL-C levels; however, literature reviews conducted in the same study did not show conclusive evidence that the HDL-C decrease could be an interaction between the 2 drugs as opposed to either drug given alone. During the clinical course of the 2 patients, the removal of either fenofibrate or rosiglitazone, while remaining on the other, resulted in HDL-C returning to or near baseline. Both patients demonstrated a score of 9 each on the Drug Interaction Probability Scale. While the results reported in the 2 patients were in agreement with some studies, they were in contrast to a number of the others that showed an increase in HDL-C with each of the drugs, or when given together resulted in an additive effects of increasing HDL-C .

B) Concomitant administration of fenofibrate and rosiglitazone demonstrated a decrease in HDL-C by 35% to 77% in case reports of 3 patients. In the first patient, after fenofibrate was added, HDL-C decreased from 46 mg/dL to 10 to 15 mg/dL. Rosiglitazone was then replaced by pioglitazone and HDL-C subsequently increased to 47 mg/dL. In the second patient, after fenofibrate was added and the dose of rosiglitazone was increased, HDL-C went down from 37 mg/dL to 23 mg/dL. Rosiglitazone was switched to pioglitazone 18 months later and HDL-C came back up to 31 mg/dL. In the third patient, after fenofibrate was added, HDL-C decreased from 42 mg/dL to 17 mg/dL. Fenofibrate was discontinued, and HDL-C increased to 43 mg/dL. In conclusion, the authors recommend alternative medications in the event of a decrease in HDL-C .

C) A retrospective review at a veteran hospital of 322 patients with type 2 diabetes mellitus receiving both a fibrate (fenofibrate or gemfibrozil) and a thiazolidinedione (TZD; rosiglitazone, pioglitazone, or troglitazone) over a period of 1 year demonstrated no difference in HDL-C from baseline to endpoint (36.8 +/- 8.5 to 40.3 +/- 11.8 mg/dL; p=0.097); however, a subset of 43 patients (13%) who experienced an unexpected decrease of 20% or greater in HDL-C was more likely to receive fenofibrate and a TZD (39 +/- 10.7 to 23.1 +/- 11.2 mg/dL; p=0.048). Patients on a fenofibrate-TZD regimen were more likely to experience this effect (odds ratio (OR), 3.08; 95% confidence interval (CI), 1.22 to 7.75; p=0.018) than those on a gemfibrozil-TZD regimen. The authors also concluded that there was a trend toward increased risk of this effect in patients treated with fenofibrate and rosiglitazone, even though the results were not statistically significant (OR, 2.82; 95% CI, 0.98 to 8; p=0.064). Among a number of limitations to this study (eg, patient sample was primarily white males from a veteran hospital), the sample size of the study may have been insufficient to power some subgroup analyses; however, an a priori estimated total sample size of 20 patients was required to detect a 20% or greater change in HDL-C .

D) Concomitant administration of fenofibrate and rosiglitazone in 5 case studies (4 males, 1 female; aged 45 to 63 years) with type 2 diabetes mellitus of 2 to 5 years in duration resulted in a 50% to 89% decrease in HDL-C levels. All 5 cases demonstrated initially stable HDL-C on fibrate treatment, but HDL-C fell when rosiglitazone was added, and HDL-C returned to or near baseline after rosiglitazone was discontinued. In one patient, HDL-C was decreased by 8% on rosiglitazone 4 mg and by 60% when the dose was increased to 8 mg. The recovery time of HDL-C after withdrawal of rosiglitazone was between 5 and 20 weeks in 4 patients, and after 4 weeks in one patient whose HDL-C rose marginally and returning to near baseline levels 10 weeks after treatment with pioglitazone. Monitoring of HDL-C levels is recommended before and after the initiation of rosiglitazone and also when the dose is increased .

E) Chart reviews of 12 HIV-negative patients with type 2 diabetes mellitus (T2DM) and 9 HIV-positive patients, with both groups on combination therapy with rosiglitazone and fenofibrate, showed a significant decrease in HDL-C compared with the control group of 12 HIV-positive patients on fibrate treatment alone. The HIV-negative with T2DM treatment group and the HIV-positive treatment group had a decrease in HDL-C by 20 +/- 17% and 33 +/- 17%, respectively, while the fibrate-alone treatment group had an increase in HDL-C by 19 +/- 13%; p less than 0.001. On cessation of either rosiglitazone or the fibrate, HDL-C returned to baseline levels. Doses of fenofibrate and rosiglitazone were not specified, and the time of drug cessation and the recovery time were not available .

Fenofibrate Overview

• Fenofibrate is used with a low-fat diet, exercise, and sometimes with other medications to reduce the amounts of fatty substances such as cholesterol and triglycerides in the blood and to increase the amount of HDL (high-density lipoprotein; a type of fatty substance that decreases the risk of heart disease) in the blood. Build-up of cholesterol and fats along the walls of the arteries (a process known as atherosclerosis) decreases the blood flow and, therefore, the oxygen supply to the heart, brain, and other parts of the body. This increases the risk of heart disease, angina (chest pain), strokes, and heart attacks. Although fenofibrate decreases the levels of fatty substances in the blood, it has not been shown to decrease the risk of heart attacks or strokes. Fenofibrate is in a class of medications called antilipemic agents. It works by speeding the natural processes that remove cholesterol from the body.

Rosiglitazone Overview

• 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).

• 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:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

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.