Fenofibrate is a lipid-lowering medication indicated as monotherapy to treat primary hyperlipidemia, mixed dyslipidemia, and hypertriglyceridemia. While this medication has been around for many years, its formulation has continued to evolve. The different fenofibrate formulations can get confusing, especially when terms such as micronized, nanoparticles, and solid dispersions get thrown into the mix. This article will give a brief overview of the pharmacodynamics of fenofibrate and then compare the non-micronized and micronized fenofibrate formulations.
Fenofibrate Pharmacodynamics & Micronization
Fenofibrate is a prodrug, which after absorption undergoes rapid hydrolysis into its active metabolite, fenofibric acid. However, fenofibrate is a neutral, lipophilic compound that has a low water solubility, making it poorly absorbed when taken orally and thus having a low bioavailability. Due to this, several different formulations of fenofibrate have been developed to increase the drug’s overall solubility.
The first technique utilized to increase the solubility of fenofibrate was that of micronization. As the technique name implies, it involves reducing the particle size of a drug to less than 10 microns, which is approximately four to ten times smaller than the conventional particle size of a drug. As the size of a particle decreases, the specific surface area increases, leading to an increase in the solubility of the particle and therefore the bioavailability of the drug. In the case of fenofibrate, the micronized formulation was found to have its bioavailability increased by ~30% when compared to the non-micronized formulation.
Similarities Between Non-Micronized and Micronized Fenofibrate
When given in equivalent doses (which will be discussed later), the efficacy of non-micronized and micronized fenofibrate is essentially the same. Both formulations have been found to lower LDL-C by 10-20%, triglycerides by 20-50%, and to increase HDL-C by 10-20%. To think about it in terms of other drugs, both formulations of fenofibrate have been reported as more effective than simvastatin or pravastatin 20 mg daily in their triglyceride-reducing and HDL-C-increasing capabilities but were found to be similarly or less effective in reducing LDL-C compared to those same drugs.
Both formulations have similar safety profiles. They both have contraindications for use in patients with severe renal impairment (CrCl < 30 mL/min or on hemodialysis), active liver or gallbladder disease, and for nursing mothers. Their adverse effect profiles are also similar, with abdominal pain, increased liver enzyme levels, and backaches being some of the most commonly reported. Limited data suggests that both fenofibrate formulations are similar in tolerability to simvastatin. Patients on either formulation should be monitored closely throughout the use of the drugs, with labs such as lipids, liver & renal function, and CBCs being collected at baseline and then periodically throughout therapy.
Since both drugs have already been on the market for quite some time, generic versions of both are currently available. According to GoodRx, a patient shouldn’t have to pay more than $20 for a 30-day bottle of either formulation in any of the available tablet sizes, and patients with insurance would likely have an even smaller copay for both.
So What’s the Difference? Micronized Versus Non-Micronized Fenofibrate
You may be thinking to yourself, “So micronized fenofibrate is basically just the exact same drug as non-micronized fenofibrate, but with smaller particle sizes. Everything else about them will be the same”. You’re 100% correct in your first statement, but surprisingly enough, there are some differences between the two.
Due to the increase in bioavailability of micronized fenofibrate, you cannot simply do a 1:1 conversion between the two. Based on bioavailability studies of the two formulations, a 100 mg non-micronized fenofibrate capsule is bioequivalent to a 67 mg micronized fenofibrate capsule. Therefore, if a patient were to be switched between the two formulations, it would be important to make sure they are given the equivalent dose to avoid causing any adverse effects.
Micronized Versus Non-micronized Administration
To aid in the absorption of non-micronized fenofibrate, it is recommended to take the medication with a high-fat meal. Doing so has been shown to increase the bioavailability of non-micronized fenofibrate significantly. However, this is counterproductive when patients are taking the medication to lower their cholesterol and triglycerides. Micronized fenofibrate does not have as strict dietary considerations, as the brand name Antara capsules can be administered without regard to meals, and the generic capsules should be administered with a meal, but it does not have to be a high-fat meal.
This article explores the differences between non-micronized and micronized fenofibrate, both of which are lipid-lowering medications used to treat primary hyperlipidemia, mixed dyslipidemia, and hypertriglyceridemia. While both formulations exhibit comparable efficacy and safety profiles, the main divergence lies in dosing and administration. Micronized fenofibrate, with its enhanced bioavailability due to its reduction in particle size, necessitates lower doses than non-micronized fenofibrate. Research has determined that a 100 mg non-micronized fenofibrate capsule is bioequivalent to a 67 mg micronized fenofibrate capsule. Moreover, unlike non-micronized fenofibrate which requires a high-fat meal with each administration, micronized fenofibrate has less strict dietary restrictions. It is important to note these differences in fenofibrate formulations, as they can affect patient outcomes.
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This article was written by Nicole Wendel, PharmD Candidate in collaboration with Eric Christianson, PharmD, BCGP, BCPS
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