Fenofibrate, a prodrug that is hydrolyzed to fenofibric acid, is an oral antilipemic agent and fibric acid derivative. Fenofibrate is indicated for the treatment of severe hypertriglyceridemia (triglycerides 500 mg/dL or greater) to reduce the risk of pancreatitis. Guidelines indicate that fenofibrate may be utilized as add-on therapy for individuals with persistent moderate to severe hypertriglyceridemia (150 to 499 mg/dL and greater than 500 mg/dL, respectively) following optimization of LDL-cholesterol lowering statin therapy. Due to a lower risk of myopathy and drug interactions, fenofibrate is preferred over gemfibrozil. While fenofibrate is FDA-approved for the treatment of primary hyperlipidemia or mixed dyslipidemia, its impact on atherosclerotic cardiovascular disease (ASCVD) risk has not been established; thus, it is typically reserved for patients with severe hypertriglyceridemia despite lifestyle modification, dietary changes, and lipid lowering therapy or as an alternative to icosapent ethyl (e.g., patients without access to icosapent ethyl). Insufficient data are available to determine the impact of fenofibrate therapy on the risk of coronary heart disease morbidity and mortality and non-cardiovascular mortality, particularly in patients receiving statin therapy and those with type 2 diabetes mellitus. A reduction in ASCVD risk has been observed in individuals with elevated triglycerides and low HDL-C concentrations. Icosapent ethyl is the preferred adjunctive therapy in individuals with persistently elevated triglycerides who require additional ASCVD risk reduction.
General Administration Information
For storage information, see specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
Oral Solid Formulations
NOTE: Fenofibrate formulations vary and are not bioequivalent.
-Fenofibrate 50 mg and 150 mg capsules (e.g., Lipofen): Administer with meals to optimize absorption. Swallow capsules whole. Do not open, crush, dissolve, or chew capsules.
-Fenofibrate 40 mg and 120 mg tablets (e.g., Fenoglide): Administer with meals to optimize absorption. Swallow tablets whole. Do not crush, dissolve, or chew tablets.
-Fenofibrate 48 mg and 145 mg tablets (e.g., Tricor): May administer without regard to meals. Swallow tablets whole. Do not crush, dissolve, or chew tablets.
-Fenofibrate 54 mg and 160 mg tablets (e.g., Lofibra): Administer with meals to optimize bioavailability. Swallow tablets whole. Do not crush, dissolve, or chew tablets.
-Fenofibrate 160 mg tablets (e.g., Triglide): May administer without regard to meals. Swallow tablets whole. Do not crush, dissolve, or chew tablets.
-Fenofibrate (micronized) 30 mg and 90 mg capsules: May administer without regard to meals. Swallow capsules whole. Do not open, crush, dissolve, or chew capsules.
-Fenofibrate (micronized) 43 mg and 130 mg capsules (e.g., Antara): May administer without regard to meals. Swallow capsules whole. Do not open, crush, dissolve, or chew capsules.
-Fenofibrate (micronized) 67 mg, 134 mg, and 200 mg capsules: Administer capsules with meals to optimize bioavailability.
Gastrointestinal side effects, such as dyspepsia, constipation, nausea, abdominal pain, diarrhea, and vomiting, are among the most commonly reported adverse effects reported with fenofibrate and generally occur in 3% to 5% of patients. Adverse GI effects reported during double-blind, placebo-controlled trials, regardless of causality and compared to placebo, include nausea (2.3% vs. 1.9%), constipation (2.1% vs. 1.4%), abdominal pain (4.6% vs. 4.4%), and diarrhea (2.3% vs. 4.1%). Cholelithiasis and cholecystitis can potentially occur during fenofibrate therapy as a result of increased cholesterol excretion into the bile. If cholelithiasis is suspected, gallbladder studies are indicated. Discontinue fenofibrate if gallstones are found during examination.
Pancreatitis has been reported in patients taking fenofibrate and other fibrates. Pancreatitis may represent a failure of efficacy in patients with severe hypertriglyceridemia, a direct drug effect, or a secondary phenomenon mediated through biliary tract stone or sludge formation with obstruction of the common bile duct. Markedly elevated levels of serum triglycerides (e.g., greater than 2,000 mg/dL) may increase the risk of developing pancreatitis. The effect of fenofibrate therapy on reducing this risk has not been adequately studied.
Hepatotoxicity or drug-induced liver injury (DILI), including liver transplantation and death have been reported with postmarketing use of fenofibrate. DILI occurred within the first weeks to several months after starting fenofibrate therapy and was reversible upon discontinuation in some cases. DILI has been characterized as hepatocellular, chronic active, and cholestatic hepatitis, as well as, cirrhosis in association with chronic active hepatitis. Reported signs and symptoms of DILI include dark urine, abnormal stool, jaundice, malaise, abdominal pain, muscle pain, weight loss, itching, and nausea. Elevated hepatic enzymes (reported as abnormal liver function tests) were reported in 7.5% of patients (vs. 1.4% placebo) during clinical trials of fenofibrate. Specifically, elevated ALT was reported in 3% of patients (vs. 1.6% placebo) and elevated AST was reported in 3.4% of patients (vs. 0.5% placebo). In a pooled analysis of 10 placebo-controlled trials, elevations of ALT of more than 3 times the upper limit of normal were seen in 5.3% of patients taking fenofibrate compared to 1.1% of patients taking placebo. In an 8-week study, the incidence of ALT or AST elevations to 3 times the upper limit of normal or greater was seen in 13% of patients receiving dosages equivalent to recommended adult dosages for the treatment of hypertriglyceridemia and was 0% in those patients receiving lower fenofibrate dosages or placebo. Cirrhosis, hepatitis, and increased total bilirubin have been reported with postmarketing use of fenofibrate. Monitor liver function, including serum transaminases (ALT, AST) and bilirubin, at baseline and periodically for the duration of fenofibrate treatment. Persistent elevations of 3 times the upper limit of normal or greater should result in discontinuation of fenofibrate therapy. Do not restart fenofibrate therapy in these patients if there is no alternative explanation for the liver injury.
Acute hypersensitivity reactions, including anaphylaxis/anaphylactoid reactions and angioedema, have been reported with postmarketing use of fenofibrate; some cases have been life-threatening requiring emergency treatment. Delayed hypersensitivity reactions, such as severe cutaneous adverse drug reactions (SCAR), Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS), have also been reported with postmarketing use of fenofibrate. These serious, delayed hypersensitivity reactions occurred within days to weeks of starting fenofibrate therapy. The cases of DRESS were associated with cutaneous reactions (e.g., rash or exfoliative dermatitis) and a combination of eosinophilia, fever, and systemic organ involvement (renal, hepatic, or respiratory). Urticaria and rash were reported in 1.1% and 1.4% of fenofibrate subjects, respectively, compared to 0% and 0.8% of placebo subjects, respectively. If SCAR is suspected, discontinue fenofibrate and treat individuals appropriately. Photosensitivity has been reported with postmarketing use of fenofibrate. Photosensitivity occurred within days to months of starting fenofibrate therapy and presented as erythematous, papulovesicular, eczematous eruptions, lichen planus-like eruptions (lichenoid), or sunburn-like eruptions. The photosensitizing effect of fenofibrate may be due to the presence of benzophenone, double benzene rings connected by a ketone group. Benzophenones, photoexcited structures, mediate phototoxic reactions through the absorption of UV light and induction of electronic excitation. Some individuals who experienced fenofibrate photosensitivity reactions reported prior photosensitivity reaction to ketoprofen. Cross-photosensitization may occur between fenofibrate and other benzophenone-containing medications or products, such as ketoprofen or certain sunscreens.
Myalgia, muscle spasms, and rhabdomyolysis have been reported with fenofibrate therapy. Fenofibrates increase the risk of myopathy and the risk of serious adverse muscle effects is higher in elderly individuals and in those with diabetes, renal impairment, and hypothyroidism. Concomitant use of fibrates, such as fenofibrate, with statins may increase the risk of these events; the risk is greatest with gemfibrozil. An increase in creatine phosphokinase (CPK) occurred in 3% of patients treated with fenofibrate monotherapy compared to 1.4% of patients treated with placebo. Myopathy should be considered in any patient with diffuse myalgias, muscle tenderness or myasthenia, and/or marked elevations of CPK concentrations. Advise patients to promptly report any unexplained muscle pain/musculoskeletal pain, tenderness, or weakness, especially if accompanied by malaise or fever; assess CPK concentrations in individuals reporting these symptoms. Discontinue fenofibrate therapy if myopathy or myositis is suspected or diagnosed or if CPK concentrations are markedly elevated. Back pain has also been reported during fenofibrate therapy at a higher rate than placebo (3.4% vs. 2.5%). Arthralgia and asthenia have been reported with postmarketing use of fenofibrate.
Mild to moderate anemia and leukopenia have been reported in patients following initiation of fenofibrate therapy. The decreases in hemoglobin, hematocrit, and white blood cell counts generally plateau with long-term treatment. Thrombocytopenia and agranulocytosis have also been reported with fenofibrate therapy. Periodic monitoring of red and white blood cell counts is recommended during the first 12 months of fenofibrate therapy.
Pulmonary embolism (PE) and deep venous thrombosis (DVT) have been reported in fenofibrate clinical trials. In the FIELD trial, PE and DVT were observed at higher rates in the fenofibrate group compared to the placebo group. Deep vein thrombosis was reported in 48 (1%) patients in the placebo group and 67 (1%) in the fenofibrate group (p=0.074); pulmonary embolism was reported in 32 (0.7%) patients in the placebo group compared to 53 (1%) in the fenofibrate group (p=0.022). In the Coronary Drug Project, suspected fatal or nonfatal PE or thrombophlebitis occurred more frequently in the clofibrate group compared to placebo (5.2% vs. 3.3% at five years; p less than 0.01).
Nervous system adverse reactions have been reported with fenofibrate therapy. During double-blind, placebo-controlled trials, headache was reported in 3.2% of subjects taking fenofibrate compared to 2.7% of subjects taking placebo.
During double-blind, placebo-controlled trials of fenofibrate, rhinitis was reported in 2.3% of patients (vs. 1.1% taking placebo), respiratory disorder was reported in 6.2% of patients (vs. 5.5% taking placebo), and influenza-like syndrome was reported in 2.1% of patients (vs. 2.7% taking placebo). Interstitial lung disease has been reported with postmarketing use of fenofibrate.
Severely decreased HDL cholesterol (HDL-C) concentration, to as low as 2 mg/dL, has been reported in diabetic and non-diabetic patients initiated on fibrate therapy. The decrease in HDL-C is mirrored by a decrease in apolipoprotein A1 and may occur within 2 weeks to years after initiation of the fibrate. The clinical significance of this decrease is unknown. HDL-C remains depressed as long as fibrate therapy is continued; however, withdrawal of the fibrate results in a rapid and sustained increase in HDL-C. Monitor HDL-C concentrations within the first few months after initiation of fenofibrate. Discontinue fenofibrate if HDL-C is severely depressed and continue monitoring until HDL-C has returned to baseline. Do not restart fibrate therapy in patients who have had a severe decrease in HDL-C.
Renal failure has been reported with postmarketing use of fenofibrate. Elevations in serum creatinine have been reported with fenofibrate therapy; however, the clinical significance of these elevations remains unknown. It is recommended to monitor renal function in patients with renal impairment. Consider renal function monitoring in patients at risk for renal insufficiency, such as the elderly and those with diabetes.
Fenofibrate impairs the absorption of vitamin B12 and may lead to vitamin B12 deficiency. Consider supplementation of vitamin B12 during fenofibrate therapy.
Insufficient data are available to determine the impact of fenofibrate therapy on the risk of coronary heart disease (cardiac disease) morbidity and mortality and non-cardiovascular mortality, particularly in patients receiving statin therapy and those with type 2 diabetes mellitus. A reduction in atherosclerotic cardiovascular disease (ASCVD) risk has been observed in individuals with elevated triglycerides and low HDL-C concentrations. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial showed combination therapy with fenofibrate and simvastatin does not reduce the rate of cardiovascular disease in high risk type 2 diabetics compared to simvastatin alone. The ACCORD trial was conducted in 10,251 high-risk patients with type 2 diabetes who were randomly assigned to either intensive or standard glycemic control; 5518 patients were randomly assigned to simvastatin plus fenofibrate or simvastatin plus placebo. The addition of fenofibrate to simvastatin did not result in a statistically significant difference in the rate of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes, during a mean follow-up of 4.7 years (2.2% in the fenofibrate groups vs. 2.4% in the placebo group; HR 0.92; 95% CI, 0.79 to 1.08, p = 0.32). The annual rate of death from any cause was 1.5% in the fenofibrate group vs. 1.6% in the placebo group (HR 0.91; 95% CI, 0.75 to 1.10, p = 0.33). Although there was a trend toward benefit in a subgroup of patients with both a triglyceride level in the highest third and an HDL cholesterol level in the lowest third, the difference was not statistically significant. Another subgroup analysis showed men seemed to benefit from the addition of fenofibrate; whereas, there was a trend toward harm in women. The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study was a 5-year randomized, placebo-controlled study evaluating the use of fenofibrate in 9795 patients with type 2 diabetes mellitus. Fenofibrate demonstrated a non-significant 11% relative reduction in the primary outcome of coronary heart disease events and a significant 11% reduction in the secondary outcome of total cardiovascular disease events (HR 0.89 (0.89-0.99), p=0.04). Further results indicate a non-significant 11% and 19% increase in total and coronary heart disease mortality, respectively, associated with the use of fenofibrate as compared to placebo. A prespecified analysis of the FIELD study to assess the effects of fenofibrate on amputation rates found the risk of first time amputation was 36% lower in patients taking fenofibrate compared with placebo (HR 0.64 (0.44-0.94), p=0.02), which is attributed to the lower risks of minor amputations (i.e., below the ankle) associated with fenofibrate versus placebo (HR 0.54 (0.34-0.85), p=0.007). Conversely, the risk of major amputations (i.e., above the ankle) did not differ significantly between the fenofibrate and placebo groups (HR 0.93 (0.53-1.62), p=0.79). Gemfibrozil monotherapy for primary and secondary prevention has demonstrated reduction in cardiovascular disease-related outcomes. Fenofibrate may be indicated for individuals with severe hypertriglyceridemia (greater than 500 mg/dL) or as add-on therapy in individuals on statin therapy who have moderate to severe hypertriglyceridemia (150 to 499 mg/dL and greater than 500 mg/dL, respectively). Due to the lower risk of myopathy and drug interactions, fenofibrate is preferred over gemfibrozil. Icosapent ethyl is preferred adjunctive therapy in individuals with persistently elevated triglycerides who require additional ASCVD risk reducton.
Fenofibrate is contraindicated in individuals with severe renal impairment (eGFR less than 30 mL/minute/1.73 m2 or CrCl 30 mL/minute or less), including renal failure or severe renal disease, and those on dialysis. A reduced fenofibrate dose is recommended for individuals with mild to moderate renal impairment (eGFR 30 to 89 mL/minute/1.73 m2 or CrCl 30 to 80 mL/minute). Elevations in serum creatinine have been reported in patients receiving fenofibrate therapy; however, the clinical significance of these elevations is unknown. Following discontinuation of therapy, serum creatinine levels typically return to baseline levels. The risk of rhabdomyolysis, myositis, and myopathy may be increased in those with renal failure receiving fenofibrate therapy. Consider monitoring renal function in individuals with renal impairment and those at risk for renal insufficiency, such as the elderly or those with diabetes.
Fenofibrate is contraindicated in patients with active hepatic disease, including those with primary biliary cirrhosis and unexplained persistent liver function abnormalities. Serious drug-induced liver injury (DILI), including liver transplantation and death, has been reported with postmarketing use of fenofibrate. DILI has been characterized as hepatocellular, chronic active, and cholestatic hepatitis, as well as, cirrhosis in association with chronic active hepatitis. Reports of DILI have occurred within the first few weeks to several months after therapy initiation and was reversible in some cases following discontinuation. In clinical trials, fenofibrate was associated with elevations in AST or ALT. Based on the incidence observed with fenofibrate therapy, increases in transaminases may be dose-related. Monitor liver function, including AST, ALT, and bilirubin, at baseline and periodically throughout fenofibrate therapy. If a patient experiences persistent LFT elevations (ALT or AST greater than 3 times the upper limit of normal or if accompanied by elevations in bilirubin) or develops signs or symptoms of liver injury, discontinue fenofibrate. Do not restart fenofibrate therapy in these patients if there is no alternative explanation for the liver injury.
Fenofibrate is contraindicated in individuals with pre-existing gallbladder disease since it may exacerbate this condition. Similar to clofibrate and gemfibrozil, fenofibrate increases cholesterol excretion and decreases bile acid excretion into bile resulting in cholesterol saturation and an increased risk of cholelithiasis and cholesterol gallstones. If gallstones develop, discontinue fenofibrate therapy.
Caution should be used when fenofibrate is used in patients with thromboembolic disease. In clinical trials, fenofibrate and clofibrate have been associated with pulmonary embolism, deep venous thrombosis, and thrombophlebitis. Fenofibrate may potentiate the effects of coumarin-type anticoagulants, thus, caution should be used when prescribing fenofibrate to patients receiving warfarin therapy.
Patients with diabetes mellitus are at increased risk for serious muscle toxicity, including myopathy and rhabdomyolysis, when treated with fenofibrate therapy. Additionally, because fenofibrate therapy has been associated with elevations in serum creatinine, renal monitoring should be considered in patients at increased risk for renal impairment including those with diabetes. Of note, fenofibrate was not shown to reduce coronary heart disease morbidity and mortality in a large, randomized controlled trial of patients with type 2 diabetes mellitus.
Use fenofibrate cautiously in patients with hypothyroidism. The risk for fenofibrate-associated serious muscle toxicity, including myopathy and rhabdomyolysis, appears to be increased in patients with hypothyroidism.
Use fenofibrate during pregnancy only if the potential benefit justifies the potential risk to the fetus. Limited data with fenofibrate use in human pregnancy are insufficient to determine an associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies, no evidence of embryofetal toxicity was observed with oral fenofibrate administration during organogenesis at doses less than or equivalent to the maximum recommended clinical dose (based on body surface area). Adverse reproductive outcomes, such as increased fetal skeletal malformations, aborted litters, post-implantation loss, and decreased pup survival, occurred at higher doses in the presence of meternal toxicity in pregnant rabbits and rats.
Fenofibrate is contraindicated during breast-feeding. Advise individuals to not breastfeed during fenofibrate treatment and for 5 days after the final dose due to the potential for serious adverse reactions in breastfed infants (e.g., disruption of infant lipid metabolism). There is no available information on the presence of fenofibrate in human milk, effects of the drug on the breastfed infant, or the effects on milk production. If pharmacotherapy is necessary for the nursing person, consider a nonabsorbable resin such as cholestyramine, colesevelam, or colestipol. These agents do not enter the bloodstream and therefore will not be excreted during lactation. However, resins bind fat-soluble vitamins, and prolonged use may result in deficiencies of these vitamins in the lactating individual and the nursing infant.
-Fibrates are expected to lower triglyceride concentrations by 20% to 55%.
-Patients should be placed on an appropriate lipid-lowering diet prior to and while receiving fenofibrate therapy. Excess body weight, excess alcohol intact, dietary indiscretion, and poor glycemic control are important factors in conditions of elevated triglycerides and should be addressed prior to initiating fenofibrate therapy.
-Monitor lipid concentrations at 4 to 12 weeks after initiation or dose adjustment.
-Insufficient data are available to determine the impact of fenofibrate therapy on the risk of coronary heart disease morbidity and mortality and non-cardiovascular mortality, particularly in patients receiving statin therapy and those with type 2 diabetes mellitus. A reduction in atherosclerotic cardiovascular disease (ASCVD) risk has been observed in individuals with elevated triglycerides and low HDL-C concentrations.
For use as an adjunct to diet for the treatment of severe hypertriglyceridemia (i.e., triglycerides 500 mg/dL or more):
Oral dosage (50 mg and 150 mg fenofibrate capsules [e.g., Lipofen]):
Adults: 50 to 150 mg PO once daily. Individualize dose based on patient response. Maximum dose is 150 mg PO once daily.
Oral dosage (40 mg and 120 mg fenofibrate tablets [e.g., Fenoglide]):
Adults: 40 mg to 120 mg PO once daily. Individualize dose based on patient response. Maximum dose is 120 mg PO once daily.
Oral dosage (48 mg and 145 mg fenofibrate tablets [Tricor]):
Adults: 48 mg to 145 mg PO once daily. Individualize dose based on patient response. Maximum dose is 145 mg PO once daily.
Oral dosage (54 mg and 160 mg fenofibrate tablets [e.g., Lofibra]):
Adults: 54 mg to 160 mg PO once daily. Individualize dose based on patient response. Maximum dose is 160 mg PO once daily.
Oral dosage (160 mg fenofibrate tablets [Triglide]):
Adults: 160 mg PO once daily. Maximum dose is 160 mg PO once daily.
Oral dosage (30 mg and 90 mg fenofibrate (micronized) capsules):
Adults: 30 mg to 90 mg PO once daily. Individualize dose based on patient response. Maximum dose is 90 mg PO once daily.
Oral dosage (43 mg and 130 mg fenofibrate (micronized) capsules [e.g., Antara]):
Adults: 43 mg to 130 mg PO once daily. Individualize dose based on patient response. Maximum dose is 130 mg PO once daily.
Oral dosage (67 mg, 134 mg, and 200 mg fenofibrate (micronized) capsules):
Adults: 67 mg to 200 mg PO once daily. Individualize dose based on patient response. Maximum dose is 200 mg PO once daily.
For the treatment of primary hypercholesterolemia or mixed dyslipidemia as an adjunct to dietary control:
NOTE: Fenofibrate may be used as add-on therapy for individuals on statin therapy who have moderate to severe hypertriglyceridemia (150 to 499 mg/dL or greater than 500 mg/dL, respectively) to reduce the risk of pancreatitis. Due to lower risk of myopathy and drug interactions, fenofibrate is preferred over gemfibrozil. Icosapent ethyl is preferred adjunctive therapy in individuals with persistently elevated triglycerides who require additional atherosclerotic cardiovascular disease (ASCVD) risk reduction.
Oral dosage (50 mg and 150 mg fenofibrate capsules [e.g., Lipofen])):
Adults: 150 mg PO once daily. Monitor lipid concentrations periodically to establish the lowest effective dose; consider reducing dose if lipid concentrations fall significantly below target range. Discontinue therapy in patients who do not have a satisfactory response after 2 months with 150 mg/day. Maximum dose is 150 mg PO once daily.
Oral dosage (40 mg and 120 mg fenofibrate tablets [e.g., Fenoglide]):
Adults: 120 mg PO once daily. Monitor lipid concentrations periodically to establish the lowest effective dose; consider reducing dose if lipid concentrations fall significantly below target range. Discontinue therapy in patients who do not have a satisfactory response after 2 months with 120 mg/day. Maximum dose is 120 mg PO once daily.
Oral dosage (48 mg and 145 mg fenofibrate tablets [e.g., Tricor]):
Adults: 145 mg PO once daily. Monitor lipid concentrations periodically to establish the lowest effective dose; consider reducing dose if lipid concentrations fall significantly below target range. Discontinue therapy in patients who do not have a satisfactory response after 2 months with 145 mg/day. Maximum dose is 145 mg PO once daily.
Oral dosage (54 mg and 160 mg fenofibrate tablets [e.g., Lofibra]):
Adults: 160 mg PO once daily. Monitor lipid concentrations periodically to establish the lowest effective dose; consider reducing dose if lipid concentrations fall significantly below target range. Discontinue therapy in patients who do not have a satisfactory response after 2 months with 160 mg/day. Maximum dose is 160 mg PO once daily.
Oral dosage (160 mg fenofibrate tablets [e.g., Triglide]):
Adults: 160 mg PO once daily. Monitor lipid concentrations periodically. Discontinue therapy in patients who do not have a satisfactory response after 2 months with 160 mg/day. Maximum dose is 160 mg PO once daily.
Oral dosage (30 mg and 90 mg fenofibrate (micronized) capsules):
Adults: 90 mg PO once daily. Monitor lipid concentrations periodically to establish the lowest effective dose; consider reducing dose if lipid concentrations fall significantly below target range. Discontinue therapy in patients who do not have a satisfactory response after 2 months with 90 mg/day. Maximum dose is 90 mg PO once daily.
Oral dosage 43 mg and 130 mg fenofibrate (micronized) capsules [e.g., Antara]):
Adults: 130 mg PO once daily. Monitor lipid concentrations periodically to establish the lowest effective dose; consider reducing dose if lipid concentrations fall significantly below target range. Discontinue therapy in patients who do not have a satisfactory response after 2 months with 130 mg/day. Maximum dose is 130 mg PO once daily.
Oral dosage (67 mg, 134 mg, and 200 mg fenofibrate (micronized) capsules):
Adults: 200 mg PO once daily. Monitor lipid concentrations periodically to establish the lowest effective dose; consider reducing dose if lipid concentrations fall significantly below target range. Discontinue therapy in patients who do not have a satisfactory response after 2 months with 200 mg/day. Maximum dose is 200 mg PO once daily.
Maximum Dosage Limits:
-Adults
90 mg to 200 mg/day; maximum dose is product-specific.
-Geriatric
90 mg to 200 mg/day; maximum dose is product-specific.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Contraindicated in patients with active liver disease, including primary biliary cirrhosis, and in patients with an unexplained, persistent liver function abnormalities.
Patients with Renal Impairment Dosing
eGFR 90 mL/minute/1.73 m2 and greater or CrCl 81 mL/minute and greater: No dose adjustment is necessary.
eGFR 30 to 89 mL/minute/1.73 m2 or CrCl 30 to 80 mL/minute: Initiate therapy at the lowest available dose for selected fenofibrate or fenofibrate (micronized) formulation. Do not increase dosage until the effects of the initial dosage on renal function and serum lipid concentrations have been fully evaluated.
eGFR less than 30 mL/minute/1.73 m2 or CrCl 30 mL/minute and lower: Contraindicated.
Intermittent hemodialysis
Contraindicated in patients undergoing dialysis.
*non-FDA-approved indication
Acarbose: (Moderate) Dose reductions and increased frequency of glucose monitoring may be required when antidiabetic agents are administered with fibric acid derivatives (e.g., clofibrate, fenofibric acid, fenofibrate, gemfibrozil). Fibric acid derivatives may enhance the hypoglycemic effects of antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion.
Alogliptin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor (DPP-4) and fibric acid derivative use; a DPP-4 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Alogliptin; Metformin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor (DPP-4) and fibric acid derivative use; a DPP-4 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant metformin and fibric acid derivative use; a metformin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Alogliptin; Pioglitazone: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor (DPP-4) and fibric acid derivative use; a DPP-4 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant pioglitazone and fenofibrate use; a pioglitazone dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Alpha-glucosidase Inhibitors: (Moderate) Dose reductions and increased frequency of glucose monitoring may be required when antidiabetic agents are administered with fibric acid derivatives (e.g., clofibrate, fenofibric acid, fenofibrate, gemfibrozil). Fibric acid derivatives may enhance the hypoglycemic effects of antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion.
Amlodipine; Atorvastatin: (Moderate) Use caution and the lowest atorvastatin dose necessary if coadministration with fenofibrate is necessary due to an increased risk of myopathy and rhabdomyolysis. Carefully weigh the potential benefits and risk of combined therapy. Use the lowest possible atorvastatin dose. Closely monitor patients for signs and symptoms of muscle pain, tenderness, or weakness especially during the initial months of therapy and during upward titration of either drug. There is no assurance that periodic monitoring of creatinine phosphokinase (CPK) will prevent the occurrence of myopathy.
Amoxicillin; Clarithromycin; Omeprazole: (Minor) At therapeutic concentrations, fenofibrate is a weak inhibitor of CYP2C19. Concomitant use of febofirbrate with CYP2C19 substrates, such as omeprazole, has not been formally studied. Fenofibrate may theoretically increase plasma concentrations of CYP2C19 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of omeprazole during coadministration with fenofibrate.
Aspirin, ASA; Omeprazole: (Minor) At therapeutic concentrations, fenofibrate is a weak inhibitor of CYP2C19. Concomitant use of febofirbrate with CYP2C19 substrates, such as omeprazole, has not been formally studied. Fenofibrate may theoretically increase plasma concentrations of CYP2C19 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of omeprazole during coadministration with fenofibrate.
Atorvastatin: (Moderate) Use caution and the lowest atorvastatin dose necessary if coadministration with fenofibrate is necessary due to an increased risk of myopathy and rhabdomyolysis. Carefully weigh the potential benefits and risk of combined therapy. Use the lowest possible atorvastatin dose. Closely monitor patients for signs and symptoms of muscle pain, tenderness, or weakness especially during the initial months of therapy and during upward titration of either drug. There is no assurance that periodic monitoring of creatinine phosphokinase (CPK) will prevent the occurrence of myopathy.
Bempedoic Acid; Ezetimibe: (Moderate) Monitor for cholelithiasis symptoms during concomitant ezetimibe and fenofibrate use. Fibrates may increase cholesterol excretion into the bile, leading to cholelithiasis. In a preclinical study in dogs, ezetimibe increased cholesterol in the gallbladder bile. If cholelithiasis is suspected, gallbladder studies are indicated and alternative lipid-lowering therapy should be considered.
Bexagliflozin: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and fibric acid derivative use; a SGLT2 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Canagliflozin: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and fibric acid derivative use; a SGLT2 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Canagliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and fibric acid derivative use; a metformin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and fibric acid derivative use; a SGLT2 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Cannabidiol: (Moderate) Consider a dose reduction of fenofibrate as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased fenofibrate exposure is possible. Fenofibrate is a UGT1A9 substrate. In vitro data predicts inhibition of UGT1A9 by cannabidiol potentially resulting in clinically significant interactions.
Chenodiol: (Major) Fibric acid derivatives (i.e., clofibrate and perhaps other lipid-lowering fibrate drugs) increase hepatic cholesterol secretion, and encourage cholesterol gallstone formation and hence may counteract the effectiveness of chenodiol.
Chlorpropamide: (Moderate) Monitor blood glucose during concomitant sulfonylurea and fenofibrate use; a sulfonylurea dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Cholestyramine: (Minor) Cholestyramine can potentially reduce the oral bioavailability of fenofibrate if these agents are administered together. Patients should take fenofibrate at least 1 hour before or 4 to 6 hours after a bile acid resin to avoid affecting the bioavailability of fenofibrate.
Colchicine: (Moderate) Monitor for myopathy during concomitant colchicine and fibric acid derivative use. Cases of myopathy, including rhabdomyolysis, have been reported with fibric acid derivatives coadministered with colchicine.
Colestipol: (Major) Based on reported interactions with gemfibrozil, colestipol or cholestyramine can potentially reduce the oral bioavailability of fenofibrate if these agents are administered together. Although the presence of a drug interaction is uncertain, patients should take fenofibrate at least 1 hour before or 4 to 6 hours after a bile acid resin to avoid affecting the bioavailability of fenofibrate.
Cyclosporine: (Moderate) The use of fibric acid derivatives, such as fenofibrate, may potentiate the risk for renal dysfunction with cyclosporine. During the concomitant use of a drug that may exhibit additive or synergistic renal impairment with cyclosporine, close monitoring of renal function (in particular serum creatinine) and cyclosporine levels should be performed. If a significant impairment of renal function occurs, the dosage of the coadministered drug should be reduced or an alternative treatment considered.
Dapagliflozin: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and fibric acid derivative use; a SGLT2 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Dapagliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and fibric acid derivative use; a metformin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and fibric acid derivative use; a SGLT2 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Dapagliflozin; Saxagliptin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor (DPP-4) and fibric acid derivative use; a DPP-4 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and fibric acid derivative use; a SGLT2 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Dipeptidyl Peptidase-4 Inhibitors: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor (DPP-4) and fibric acid derivative use; a DPP-4 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Dulaglutide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and fibric acid derivative use; an incretin mimetic dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Empagliflozin: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and fibric acid derivative use; a SGLT2 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Empagliflozin; Linagliptin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor (DPP-4) and fibric acid derivative use; a DPP-4 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and fibric acid derivative use; a SGLT2 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Empagliflozin; Linagliptin; Metformin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor (DPP-4) and fibric acid derivative use; a DPP-4 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant metformin and fibric acid derivative use; a metformin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and fibric acid derivative use; a SGLT2 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Empagliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and fibric acid derivative use; a metformin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and fibric acid derivative use; a SGLT2 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Ertugliflozin: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and fibric acid derivative use; a SGLT2 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Ertugliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and fibric acid derivative use; a metformin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and fibric acid derivative use; a SGLT2 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Ertugliflozin; Sitagliptin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor (DPP-4) and fibric acid derivative use; a DPP-4 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and fibric acid derivative use; a SGLT2 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Exenatide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and fibric acid derivative use; an incretin mimetic dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Ezetimibe: (Moderate) Monitor for cholelithiasis symptoms during concomitant ezetimibe and fenofibrate use. Fibrates may increase cholesterol excretion into the bile, leading to cholelithiasis. In a preclinical study in dogs, ezetimibe increased cholesterol in the gallbladder bile. If cholelithiasis is suspected, gallbladder studies are indicated and alternative lipid-lowering therapy should be considered.
Ezetimibe; Simvastatin: (Moderate) Fenofibrate and simvastatin should administered concomitantly only with caution. Fenofibrate may increase the risk of myopathy, rhabdomyolysis, and acute renal failure; this risk is increased with higher doses of simvastatin. The serious risk of myopathy or rhabdomyolysis should be weighed carefully versus the benefits of combined 'statin' and fibrate therapy; there is no assurance that periodic monitoring of CK will prevent the occurrence of severe myopathy and renal damage. (Moderate) Monitor for cholelithiasis symptoms during concomitant ezetimibe and fenofibrate use. Fibrates may increase cholesterol excretion into the bile, leading to cholelithiasis. In a preclinical study in dogs, ezetimibe increased cholesterol in the gallbladder bile. If cholelithiasis is suspected, gallbladder studies are indicated and alternative lipid-lowering therapy should be considered.
Fluvastatin: (Major) Use caution when coadministering fluvastatin and fenofibrate. The risk of myopathy increases when HMG-Co-A reductase inhibitors ('statins'), including fluvastatin, are administered concurrently with fibric acid derivatives. The serious risk of myopathy or rhabdomyolysis should be weighed carefully versus the benefits of combined 'statin' and fibrate therapy; there is no assurance that periodic monitoring of CK will prevent the occurrence of severe myopathy and renal damage.
Glimepiride: (Moderate) Monitor blood glucose during concomitant sulfonylurea and fenofibrate use; a sulfonylurea dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Glipizide: (Moderate) Monitor blood glucose during concomitant sulfonylurea and fenofibrate use; a sulfonylurea dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Glipizide; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and fibric acid derivative use; a metformin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant sulfonylurea and fenofibrate use; a sulfonylurea dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Glyburide: (Moderate) Monitor blood glucose during concomitant sulfonylurea and fenofibrate use; a sulfonylurea dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Glyburide; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and fibric acid derivative use; a metformin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant sulfonylurea and fenofibrate use; a sulfonylurea dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Incretin Mimetics: (Moderate) Monitor blood glucose during concomitant incretin mimetic and fibric acid derivative use; an incretin mimetic dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Aspart: (Moderate) Monitor blood glucose during concomitant fibric acid derivatives and insulin use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Aspart; Insulin Aspart Protamine: (Moderate) Monitor blood glucose during concomitant fibric acid derivatives and insulin use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Degludec: (Moderate) Monitor blood glucose during concomitant fibric acid derivatives and insulin use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Degludec; Liraglutide: (Moderate) Monitor blood glucose during concomitant fibric acid derivatives and insulin use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant incretin mimetic and fibric acid derivative use; an incretin mimetic dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Detemir: (Moderate) Monitor blood glucose during concomitant fibric acid derivatives and insulin use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Glargine: (Moderate) Monitor blood glucose during concomitant fibric acid derivatives and insulin use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Glargine; Lixisenatide: (Moderate) Monitor blood glucose during concomitant fibric acid derivatives and insulin use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant incretin mimetic and fibric acid derivative use; an incretin mimetic dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Glulisine: (Moderate) Monitor blood glucose during concomitant fibric acid derivatives and insulin use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Lispro: (Moderate) Monitor blood glucose during concomitant fibric acid derivatives and insulin use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Lispro; Insulin Lispro Protamine: (Moderate) Monitor blood glucose during concomitant fibric acid derivatives and insulin use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin, Inhaled: (Moderate) Monitor blood glucose during concomitant fibric acid derivatives and insulin use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulins: (Moderate) Monitor blood glucose during concomitant fibric acid derivatives and insulin use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Isophane Insulin (NPH): (Moderate) Monitor blood glucose during concomitant fibric acid derivatives and insulin use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Linagliptin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor (DPP-4) and fibric acid derivative use; a DPP-4 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Linagliptin; Metformin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor (DPP-4) and fibric acid derivative use; a DPP-4 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant metformin and fibric acid derivative use; a metformin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Liraglutide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and fibric acid derivative use; an incretin mimetic dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Lixisenatide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and fibric acid derivative use; an incretin mimetic dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Lovastatin: (Moderate) Concurrent use of fenofibrate and lovastatin may increase the risk of myopathy, rhabdomyolysis, and acute renal failure. The serious risk of myopathy and rhabdomyolysis should be weighed carefully against the benefit of further alteration in lipid concentrations by the combined use of fenofibrate or fenofibric acid and lovastatin.
Metformin: (Moderate) Monitor blood glucose during concomitant metformin and fibric acid derivative use; a metformin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Metformin; Repaglinide: (Moderate) Dose reductions and increased frequency of glucose monitoring may be required when antidiabetic agents are administered with fibric acid derivatives (e.g., clofibrate, fenofibric acid, fenofibrate, gemfibrozil). Fibric acid derivatives may enhance the hypoglycemic effects of antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion. (Moderate) Monitor blood glucose during concomitant metformin and fibric acid derivative use; a metformin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Metformin; Saxagliptin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor (DPP-4) and fibric acid derivative use; a DPP-4 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant metformin and fibric acid derivative use; a metformin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Metformin; Sitagliptin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor (DPP-4) and fibric acid derivative use; a DPP-4 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant metformin and fibric acid derivative use; a metformin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Miglitol: (Moderate) Dose reductions and increased frequency of glucose monitoring may be required when antidiabetic agents are administered with fibric acid derivatives (e.g., clofibrate, fenofibric acid, fenofibrate, gemfibrozil). Fibric acid derivatives may enhance the hypoglycemic effects of antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion.
Nateglinide: (Moderate) Dose reductions and increased frequency of glucose monitoring may be required when antidiabetic agents are administered with fibric acid derivatives (e.g., clofibrate, fenofibric acid, fenofibrate, gemfibrozil). Adjust nateglinide dosage if clinically indicated. Fibric acid derivatives may enhance the hypoglycemic effects of antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion.
Omeprazole: (Minor) At therapeutic concentrations, fenofibrate is a weak inhibitor of CYP2C19. Concomitant use of febofirbrate with CYP2C19 substrates, such as omeprazole, has not been formally studied. Fenofibrate may theoretically increase plasma concentrations of CYP2C19 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of omeprazole during coadministration with fenofibrate.
Omeprazole; Amoxicillin; Rifabutin: (Minor) At therapeutic concentrations, fenofibrate is a weak inhibitor of CYP2C19. Concomitant use of febofirbrate with CYP2C19 substrates, such as omeprazole, has not been formally studied. Fenofibrate may theoretically increase plasma concentrations of CYP2C19 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of omeprazole during coadministration with fenofibrate.
Omeprazole; Sodium Bicarbonate: (Minor) At therapeutic concentrations, fenofibrate is a weak inhibitor of CYP2C19. Concomitant use of febofirbrate with CYP2C19 substrates, such as omeprazole, has not been formally studied. Fenofibrate may theoretically increase plasma concentrations of CYP2C19 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of omeprazole during coadministration with fenofibrate.
Paclitaxel: (Minor) Paclitaxel is a substrate of CYP2C8, and fenofibrate is a CYP2C8 inhibitor. If coadministration is necessary, use caution and monitor for increased paclitaxel side effects, including myelosuppression and peripheral neuropathy.
Pioglitazone: (Moderate) Monitor blood glucose during concomitant pioglitazone and fenofibrate use; a pioglitazone dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Pioglitazone; Glimepiride: (Moderate) Monitor blood glucose during concomitant pioglitazone and fenofibrate use; a pioglitazone dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant sulfonylurea and fenofibrate use; a sulfonylurea dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Pioglitazone; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and fibric acid derivative use; a metformin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant pioglitazone and fenofibrate use; a pioglitazone dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Pitavastatin: (Moderate) Clinical practice guidelines state the concurrent use of fenofibrate and pitavastatin is reasonable and preferred over gemfibrozil if statin/fibrate combination therapy is indicated. However, because combination therapy increases the risk of myopathy, caution is advised.
Pramlintide: (Moderate) Dose reductions and increased frequency of glucose monitoring may be required when antidiabetic agents are administered with fibric acid derivatives (e.g., clofibrate, fenofibric acid, fenofibrate, gemfibrozil). Fibric acid derivatives may enhance the hypoglycemic effects of antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion.
Pravastatin: (Moderate) Monitor for an increase in pravastatin-related adverse reactions if coadministration with fenofibrate is necessary. Concomitant use increases the risk for rhabdomyolysis and has been shown to increase the overall exposure of pravastatin by 13%.
Probenecid; Colchicine: (Moderate) Monitor for myopathy during concomitant colchicine and fibric acid derivative use. Cases of myopathy, including rhabdomyolysis, have been reported with fibric acid derivatives coadministered with colchicine.
Raltegravir: (Moderate) Raltegravir use has been associated with elevated creatinine kinase concentrations; myopathy and rhabdomyolysis have been reported. Use raltegravir cautiously with drugs that increase the risk of myopathy or rhabdomyolysis such as fibric acid derivatives.
Red Yeast Rice: (Major) Since compounds in red yeast rice are chemically similar to and possess actions similar to lovastatin, patients should avoid this dietary supplement if they currently take drugs known to increase the risk of myopathy (e.g., fibric acid derivatives (gemfibrozil, fenofibrate, clofibrate)) when coadministered with HMG-CoA reductase inhibitors.
Regular Insulin: (Moderate) Monitor blood glucose during concomitant fibric acid derivatives and insulin use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Regular Insulin; Isophane Insulin (NPH): (Moderate) Monitor blood glucose during concomitant fibric acid derivatives and insulin use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Repaglinide: (Moderate) Dose reductions and increased frequency of glucose monitoring may be required when antidiabetic agents are administered with fibric acid derivatives (e.g., clofibrate, fenofibric acid, fenofibrate, gemfibrozil). Fibric acid derivatives may enhance the hypoglycemic effects of antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion.
Rosiglitazone: (Moderate) Dose reductions and increased frequency of glucose monitoring may be required when antidiabetic agents are administered with fibric acid derivatives (e.g., clofibrate, fenofibric acid, fenofibrate, gemfibrozil). Fibric acid derivatives may enhance the hypoglycemic effects of antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion.
Rosuvastatin: (Moderate) Clinical practice guidelines state the concurrent use of fenofibrate and rosuvastatin is reasonable and preferred over gemfibrozil if statin/fibrate combination therapy is indicated. However, because combination therapy increases the risk of myopathy, caution is advised.
Rosuvastatin; Ezetimibe: (Moderate) Clinical practice guidelines state the concurrent use of fenofibrate and rosuvastatin is reasonable and preferred over gemfibrozil if statin/fibrate combination therapy is indicated. However, because combination therapy increases the risk of myopathy, caution is advised. (Moderate) Monitor for cholelithiasis symptoms during concomitant ezetimibe and fenofibrate use. Fibrates may increase cholesterol excretion into the bile, leading to cholelithiasis. In a preclinical study in dogs, ezetimibe increased cholesterol in the gallbladder bile. If cholelithiasis is suspected, gallbladder studies are indicated and alternative lipid-lowering therapy should be considered.
Saxagliptin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor (DPP-4) and fibric acid derivative use; a DPP-4 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Semaglutide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and fibric acid derivative use; an incretin mimetic dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
SGLT2 Inhibitors: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and fibric acid derivative use; a SGLT2 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Simvastatin: (Moderate) Fenofibrate and simvastatin should administered concomitantly only with caution. Fenofibrate may increase the risk of myopathy, rhabdomyolysis, and acute renal failure; this risk is increased with higher doses of simvastatin. The serious risk of myopathy or rhabdomyolysis should be weighed carefully versus the benefits of combined 'statin' and fibrate therapy; there is no assurance that periodic monitoring of CK will prevent the occurrence of severe myopathy and renal damage.
Sitagliptin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor (DPP-4) and fibric acid derivative use; a DPP-4 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Sotagliflozin: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and fibric acid derivative use; a SGLT2 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Sulfonylureas: (Moderate) Monitor blood glucose during concomitant sulfonylurea and fenofibrate use; a sulfonylurea dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Tacrolimus: (Moderate) Coadministration of fenofibrate and tacrolimus may result in deterioration of renal function. Tacrolimus can produce nephrotoxicity with decreases in creatinine clearance and increaess in serum creatinine. Because the primary elimination route of fenofibrate is renal excretion, the benefits and risks of using fenofibrate with tacrolimus should be carefully considered, and the lowest effective dose employed with monitoring of renal function.
Tirzepatide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and fibric acid derivative use; an incretin mimetic dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Ursodeoxycholic Acid, Ursodiol: (Major) Fibric acid derivatives increase hepatic cholesterol secretion, and encourage cholesterol gallstone formation and hence may counteract the effectiveness of ursodeoxycholic acid, ursodiol.
Warfarin: (Moderate) Fenofibrate potentiates the effects of warfarin and other oral anticoagulants, resulting in increased prothrombin times. Fibrates have been shown to decrease vitamin K dependent coagulation factor synthesis. Since these drugs are also highly protein-bound, it is possible that fenofibrate displaces warfarin from protein-binding sites as a potential mechanism. Case reports of significant effects on warfarin exist for all fibrate drugs. Three clinical case reports of fenofibrate and warfarin interactions have been reported in post-marketing surveillance of fenofibrate in the US and Europe. In one case, a 47 year old male who had been stable over a course of 20 weeks on his prescribed warfarin dose was admitted to the hospital one week after beginning treatment for hypertriglyceridemia with fenofibrate 201 mg/day. He presented with epigastric discomfort and hematuria. His INR on admission was > 8.5 (previously stabilized at 2 to 2.5 prior to fenofibrate). The patient received treatment with phytonadione and discontinuation of the medications. He was discharged 2 days later, but agreed to be rechallenged under a controlled protocol to confirm the interaction of the fenofibrate with his warfarin. After stabilization of his warfarin dose for 3 weeks, fenofibrate was restarted, and the patient was rechallenged on 2 occasions. Both times, an increase in INR above the therapeutic range occurred. Patients receiving warfarin in conjunction with fenofibrate should have frequent prothrombin time and INR determinations until it has been determined that the INR has been stabilized. A reduction in warfarin dose may be necessary.
Fenofibric acid, the active component of fenofibrate, is a synthetic ligand for peroxisome proliferator activated receptor-alpha (PPAR-alpha). The PPARs are part of the nuclear hormone superfamily and are ligand-activated transcription factors involved in many metabolic effects, such as lipid and glucose metabolism. PPAR-alpha is expressed in tissues involved in the metabolism of fatty acids, specifically the liver, heart, kidney and muscle. Fenofibric acid activates PPAR-alpha increasing lipoprotein lipase (LPL) activity and decreasing production of apoprotein C-III (apo-C-III), an inhibitor of lipoprotein lipase, which increases lipolysis of triglycerides from chylomicrons and very low-density lipoproteins (VLDL) and decreases plasma concentrations of triglyceride-rich particles. Triglyceride reduction alters the size and composition of LDL, changing it from small, dense particles to large buoyant particles that have a greater affinity for cholesterol receptors and are catabolized quicker. In addition, PPAR-alpha activation increases apoprotein A-I, apoprotein A-II, and high-density lipoprotein (HDL) cholesterol. Fenofibric acid also reduces serum uric acid levels by increasing urinary excretion of uric acid.
Fenofibrate is administered orally. It is a prodrug that is rapidly and completely hydrolyzed by plasma esterases to fenofibric acid following oral administration. Following fenofibrate administration, fenofibric acid steady state concentrations are attained within 5 to 9 days and these concentrations are approximately double those after a single oral dose. In normal and dyslipidemic patients, fenofibric acid is highly protein bound (approximately 99%). Fenofibric acid is primarily conjugated with glucuronic acid; however, a small portion is reduced at the carbonyl moiety to a benzhydrol metabolite, which subsequently undergoes conjugation with glucuronic acid. Primary route of excretion is via the urine as fenofibric acid and fenofibric acid glucuronide. Approximately 60% of a dose is excreted in the urine, and 25% excreted in the feces. The elimination half-life of fenofibrate is 16 to 23 hours.
Affected cytochrome P450 isoenzymes: CYP2C8, CYP2C9, CYP2C19, CYP2A6
Fenofibrate and fenofibric acid are weak inhibitors of CYP2C8, CYP2C19 and CYP2A6, and mild-to-moderate inhibitors of CYP2C9 at therapeutic concentrations. Fenofibrate is not metabolized by CYP isoenzymes.
-Route-Specific Pharmacokinetics
Oral Route
-Fenofibrate 50 mg and 150 mg capsules (e.g., Lipofen): Peak plasma concentrations of fenofibric acid occur within 5 hours after fenofibrate administration. When fenofibrate was administered with a high-fat meal and low-fat meal, the extent of absorption was increased by 58% and 25%, respectively, compared to administration under fasting conditions. In a single dose and multiple dose bioavailability study with fenofibrate 200 mg capsules, the extent of absorption (AUC) of fenofibric acid was 42% greater and the Cmax was 73% greater following multiple doses compared to single-dose administration. While the dose-related increase in the AUC of fenofibric acid was less than proportional, the increase in Cmax was proportional. The rate and extent of fenofibric acid absorption when administered with a high-fat meal and low-fat meal is equivalent for fenofibrate 150 mg capsules and fenofibrate (Tricor) 160 mg tablets.
-Fenofibrate 40 mg and 120 mg tablets (e.g., Fenoglide): Peak plasma concentrations of fenofibric acid occur within 2 to 3 hours after fenofibrate administration. There is no change in the AUC of fenofibric acid when fenofibrate tablets are administered with a high-fat meal; however, the mean Cmax increases by 44% compared to administration under fasting conditions. Fenofibric acid concentrations following a single dose of fenofibrate 120 mg tablets are equivalent to those of fenofibrate 130 mg capsules under fasting conditions. Three fenofibrate 40 mg tablets are considered to be equivalent to a single 120 mg tablet. This formulation should be taken with food.
-Fenofibrate 48 mg and 145 mg tablets (e.g., Tricor): Peak plasma concentrations of fenofibric acid occur within 6 to 8 hours after fenofibrate administration. The AUC and Cmax of fenofibrate 145 mg are not significantly different when administered under fasting versus non-fasting conditions. Plasma concentrations after administration of three 48 mg tablets or one 145 mg tablet are equivalent under fed conditions to one fenofibrate (micronized) 200 mg capsule. This formulation may be administered without regard to meals.[29fen393]
-Fenofibrate 54 mg and 160 mg tablets (e.g., Lofibra): Peak plasma concentrations of fenofibric acid occur within 6 to 8 hours after fenofibrate administration. Compared to fasting conditions, the extent of absorption is increased by approximately 35% with fenofibrate administration under fed conditions. This formulation should be taken with food.
-Fenofibrate 160 mg tablets (e.g., Triglide): Peak plasma concentrations of fenofibric acid occur an average of 3 hours after fenofibrate administration. Fenofibrate 160 mg tablets and fenofibrate (micronized) 200 mg capsules have comparable bioavailability. The extent of absorption is comparable between fed and fasted conditions; however, food increases the rate of absorption by approximately 55%. This formulation may be taken without regard to meals.
-Fenofibrate (micronized) 30 mg and 90 mg capsules: Peak plasma concentrations of fenofibric acid occur within 2 to 6 hours after fenofibrate 90 mg administration. When fenofibrate 30 mg is administered with a high-fat meal, the fenofibric acid AUC increases by 26.7% and the Cmax by 15.35% compared to the fasting state. This formulation may be taken without regard to meals.
-Fenofibrate (micronized) 43 mg and 130 mg capsules (e.g., Antara): Peak plasma concentrations occur within 4 to 8 hours after administration. There is a less than dose-proportional increase in systemic exposure of fenofibric acid from 43 mg to 130 mg under fasting conditions. Under fasting conditions, three 43 mg capsules are dose equivalent to one 130 mg capsule. Extent of absorption is unaffected when taken in a fasted state or with a low-fat meal; however, Cmax increased in the presence of a low-fat meal. In the presence of a high-fat meal, there is a 26% increase in AUC and 108% increase in Cmax relative to fasting state. This formulation may be taken without regard to meals.
-Fenofibrate (micronized) 67 mg, 134 mg, and 200 mg capsules: Peak plasma concentrations of fenofibric acid occur within 6 to 8 hours after administration. Absorption is increased by approximately 35% under fed as compared to fasting conditions; thus, administer with a meal. Following administration to healthy volunteers, blood levels demonstrate that micronized fenofibrate 67 mg is bioequivalent to non-micronized fenofibrate 100 mg. In addition, three 67 mg capsules are bioequivalent to one 200 mg capsule.
-Special Populations
Hepatic Impairment
Fenofibrate has not been studied in patients with hepatic impairment.
Renal Impairment
The pharmacokinetics of fenofibrate are altered in patients with mild, moderate, and severe renal impairment. Compared to healthy subjects, patients with severe renal impairment (CrCl less than 30 mL/minute or estimated Glomerular filtration rate [eGFR] less than 30 mL/minute/1.73 m2) have a 2.7-fold increase in exposure of fenofibric acid and accumulation of fenofibric acid during chronic dosing compared to healthy subjects. Patients with mild to moderate renal impairment (CrCl 30 to 80 mL/minute or eGFR 30 to 59 mL/minute/1.73 m2) have similar exposure to fenofibric acid but experience an increase in the half-life compared to healthy subjects. Fenofibrate metabolites are not removed by hemodialysis. Fenofibrate is contraindicated in individuals with severe renal impairment, including end-stage renal disease, or those receiving dialysis. Dose reduction is required in patients with mild or moderate renal impairment.
Pediatrics
Fenofibrate pharmacokinetics have not been studied in the pediatric population.
Geriatric
Following a single oral dose of fenofibrate, oral clearance of fenofibric acid is 1.2 L/hour for elderly individuals (77 to 87 years of age) and 1.1 L/hour for young adults. Thus, elderly and young adults may use an equivalent fenofibrate dose.
Gender Differences
Gender has not been shown to have an effect on the pharmacokinetics of fenofibrate.
Ethnic Differences
While the influence of race on fenofibrate pharmacokinetics has not been studied, it is not metabolized by enzymes known for exhibiting inter-ethnic variability.