Should fenofibrate be taken with food in adults treated for hypertriglyceridemia or mixed dyslipidemia?

Should Fenofibrate Be Taken With Food?

Yes, fenofibrate tablets should be taken with meals to optimize bioavailability, according to FDA labeling. 1

FDA-Approved Administration Guidelines

The FDA prescribing information explicitly states that fenofibrate tablets should be given with meals, thereby optimizing the bioavailability of the medication. 1 This is the definitive recommendation from the drug label and takes priority over other considerations.

Why Food Matters for Standard Formulations

• Standard fenofibrate formulations are highly lipophilic and virtually insoluble in water, making them poorly absorbed when taken on an empty stomach 2
• Early formulations required coadministration with meals to maximize bioavailability 2
• The absolute bioavailability cannot be determined due to fenofibrate being virtually insoluble in aqueous media suitable for injection 3

Formulation-Specific Considerations

Not all fenofibrate formulations are equivalent, and this is a critical point to prevent medication errors:

• Micronized and nanoparticle formulations with reduced particle sizes have greater solubility and improved bioavailability, and some can be given irrespective of food 2
• Fenofibric acid (the active metabolite) can be taken without regard to meals, is absorbed throughout the gastrointestinal tract, and has the highest bioavailability among marketed formulations 2
• Fenofibrate-coated microgranules (FF-muG) 130 mg showed equivalent efficacy whether taken with or without food in patients with hypertriglyceridemia 4
• Different formulations are not equivalent on a milligram-to-milligram basis (e.g., 67 mg and 200 mg micronized capsules are equivalent to 54 mg and 160 mg suprabioavailable tablets, respectively) 3

Clinical Evidence on Food Effect

• In a randomized controlled trial, fenofibrate-coated microgranules 130 mg showed no inequivalence in triglyceride-lowering effects when administered with versus without food (36.7% vs 36.6% reduction, both P < 0.001 vs placebo) 4
• Fenofibric acid 105 mg met FDA bioequivalence criteria to fenofibrate 145 mg in both fed and fasted states 5

Practical Algorithm for Administration

For standard fenofibrate tablets (most common formulation):

1. Instruct patients to take fenofibrate with their largest meal of the day 1
2. This ensures optimal absorption and consistent drug levels 1

For newer formulations (fenofibric acid or specific micronized formulations):

1. Check the specific product labeling, as some can be taken without regard to meals 2
2. Healthcare providers must recognize which formulation is prescribed to prevent underdosing or overdosing 2

Common Pitfall to Avoid

The most critical error is assuming all fenofibrate formulations are interchangeable. 2 Always verify the specific formulation prescribed, as food requirements, dosing equivalencies, and bioavailability vary substantially between products. When switching formulations, do not use milligram-to-milligram equivalence. 2, 3