Fibrates are a type of amphipathic carboxylic acid that treat hypertriglyceridemia. They work by reducing the liver’s production of VLDL particles that carry triglycerides to tissues and accelerating the body’s removal of triglycerides. Due to this mechanism of action, they significantly lower triglyceride levels (50-70%), are moderately effective in increasing HDL (5-20%), and do not lower LDL to a large extent.
Because of the primary effect on triglycerides, fibrates are indicated when patients have triglyceride levels of 500 to 999mg/dL and LDL levels are within goal. They should be used in combination with lifestyle modification and other lipid-lowering medications if the patient is at high risk for ASCVD. In the high-risk ASCVD group, they will generally be added if triglycerides are still elevated despite statin and icosapent ethyl use. In patients not at high ASCVD risk, fibrates are generally the first choice of therapy to lower triglycerides. Goal TG levels 2-3 months after initiating a fibrate are <500mg/dL.
They are often prescribed with statins for the primary goal of lowering triglycerides. They can also help mildly increase HDL and lower LDL. Gemfibrozil should not be combined with statins as it interferes with statin breakdown, increasing the risk of muscle damage (rhabdomyolysis). Fenofibrate has a lower risk of interacting with statins and is the drug of choice when combining fibrates and statins. Creatinine phosphokinase should be monitored especially in patients with diabetes, hypothyroidism, or renal failure.
The most common side effects from fibrates are GI in nature and include constipation, diarrhea, stomach upset. Gallstones are rare but can occur typically after several years of use. Liver injury is another rare adverse effect. It is suggested that serum ALT, AST, and total bilirubin is monitored at baseline and throughout therapy as clinically indicated.
Fibrates increase the effectiveness of blood thinners. Dose adjust warfarin (decrease 30%) and monitor INR closely if adding a fibrate to prevent excessive bleeding. Use is contraindicated in patients with hepatic impairment and doses need to be adjusted for renal impairment and geriatric patients.
Fenofibrate and gemfibrozil are the only fibrates approved in the United States. Fenofibrate comes in three different forms, a nanocrystal tablet, a micronized capsule, and fenofibric acid. The micronized capsule must be taken with supper. The other dosage forms do not have to be taken with food. Gemfibrozil only has one dosage form that is given twice a day before breakfast and dinner.
Article written by Madison Bonn, PharmD Candidate in collaboration with Eric Christianson, PharmD, BCPS, BCGP
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