Fibrates are lipid-lowering agents that are primarily used to reduce triglycerides. They are most beneficial in patients with significantly elevated triglyceride levels, particularly those above 500 mg/dL, where the primary clinical goal is reducing the risk of pancreatitis rather than aggressive LDL lowering for cardiovascular protection purposes (i.e., statins). Pharmacists should remember that LDL responses to fibrates can be variable, especially when baseline triglycerides are very high. I recently put together a podcast episode on fibrates if you’d prefer to listen to some of these practice pearls.
One of the most important practice considerations with fibrates is their interaction with statins. Gemfibrozil, in particular, significantly increases statin concentrations and is associated with a higher risk of myopathy and rhabdomyolysis. When a fibrate is needed in a patient already receiving statin therapy, fenofibrate is generally preferred because it has a lower risk of clinically significant drug–drug interactions and a safer profile when used in combination.
Gastrointestinal adverse effects are among the most commonly reported side effects of fibrate therapy. Patients may experience dyspepsia, abdominal discomfort, nausea, or diarrhea, which are typically mild but can still affect adherence. Pharmacists should routinely assess for new or worsening gastrointestinal symptoms when fibrates are initiated or doses are adjusted. I’ve seen this cause the prescribing cascade a handful of times (addition of Maalox, Tums, PPIs, H2 blockers, etc. to reduce GI adverse effects).
Another key counseling point is the increased risk of gallstone formation associated with fibrates. These agents can alter bile composition by increasing cholesterol saturation, which may promote gallstone development. Caution is warranted in patients with a history of gallbladder disease, and new biliary symptoms should prompt further evaluation.
Overall, fenofibrate is often favored over gemfibrozil in clinical practice due to its improved safety profile and flexibility in lipid-lowering regimens. Its lower interaction risk, particularly with statins, makes it a more practical option for many patients who require combination therapy, reinforcing its role as the preferred fibrate in modern dyslipidemia management. Once daily dosing of fenofibrate in addition to a lower interaction risk with statins are the two primary advantages over gemfibrozil.
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