Lofibra

Fibric Acid Derivatives/Fibrates

For storage information, see specific product information within the How Supplied section.
 
NOTE: Patients should be placed on an appropriate lipid-lowering diet before and while receiving fenofibrate. Excess body weight, excess alcohol intake, dietary indiscretion, and poor glycemic control are important factors in conditions of elevated triglycerides and should be addressed prior to instituting fenofibrate therapy.

NOTE: Fenofibrate formulations vary and are not bioequivalent.
Antara fenofibrate micronized capsules (30 and 90 mg): May administer without regard to meals.
Generic equivalent to the original Tricor tablet formulation (54 and 160 mg tablets): Administer with meals to optimize bioavailability. NOTE: This original Abbott Tricor brand formulation has been discontinued. A generic equivalent was approved in May 2005; availability is pending.
Lipofen fenofibrate capsules (50, 100, and 150 mg capsules): Administer with meals to optimize absorption.
Lofibra fenofibrate micronized capsules (67, 134, and 200 mg): Administer with meals to optimize bioavailability.
New Tricor formulation of fenofibrate tablets (48 and 145 mg): May administer without regard to meals.
Triglide tablets, a reformulation of fenofibrate (50 and 160 mg): Instruct patient not to consume chipped or broken tablets. May administer without regard to meals. In a single-dose pharmacokinetics study in healthy volunteers, the Triglide 160 mg tablet was shown to have comparable bioavailability to a single dose of 200 mg fenofibrate capsule, micronized. However, Triglide 160 mg tablet exhibits a 32% higher rate of absorption compared to the 200 mg micronized fenofibrate capsule under low-fat fed conditions. The extent of absorption of Triglide is comparable between fed and fasted conditions; however, food increases the rate of absorption by approximately 55%.

thrombosis / Delayed / 1.0-1.0
pulmonary embolism / Delayed / 1.0-1.0
peptic ulcer / Delayed / Incidence not known
angioedema / Rapid / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
serious hypersensitivity reactions or anaphylaxis / Rapid / Incidence not known
cholecystitis / Delayed / Incidence not known
hepatotoxicity / Delayed / Incidence not known
cirrhosis / Delayed / Incidence not known
rhabdomyolysis / Delayed / Incidence not known
agranulocytosis / Delayed / Incidence not known
pancreatitis / Delayed / Incidence not known
bronchospasm / Rapid / Incidence not known
atrial fibrillation / Early / Incidence not known
arrhythmia exacerbation / Early / Incidence not known
myocardial infarction / Delayed / Incidence not known

elevated hepatic enzymes / Delayed / 3.0-13.0
constipation / Delayed / 2.1-2.1
colitis / Delayed / Incidence not known
esophagitis / Delayed / Incidence not known
gastritis / Delayed / Incidence not known
bleeding / Early / Incidence not known
contact dermatitis / Delayed / Incidence not known
skin ulcer / Delayed / Incidence not known
cholelithiasis / Delayed / Incidence not known
hepatitis / Delayed / Incidence not known
jaundice / Delayed / Incidence not known
myasthenia / Delayed / Incidence not known
myopathy / Delayed / Incidence not known
lymphadenopathy / Delayed / Incidence not known
anemia / Delayed / Incidence not known
thrombocytopenia / Delayed / Incidence not known
leukopenia / Delayed / Incidence not known
eosinophilia / Delayed / Incidence not known
depression / Delayed / Incidence not known
hypertonia / Delayed / Incidence not known
interstitial lung disease / Delayed / Incidence not known
dyspnea / Early / Incidence not known
hypotension / Rapid / Incidence not known
sinus tachycardia / Rapid / Incidence not known
migraine / Early / Incidence not known
palpitations / Early / Incidence not known
angina / Early / Incidence not known
chest pain (unspecified) / Early / Incidence not known
hypertension / Early / Incidence not known
phlebitis / Rapid / Incidence not known
blurred vision / Early / Incidence not known
amblyopia / Delayed / Incidence not known
conjunctivitis / Delayed / Incidence not known
cataracts / Delayed / Incidence not known
hyperuricemia / Delayed / Incidence not known
gout / Delayed / Incidence not known
candidiasis / Delayed / Incidence not known
nephrolithiasis / Delayed / Incidence not known
dysuria / Early / Incidence not known
cystitis / Delayed / Incidence not known
hypoglycemia / Early / Incidence not known
diabetes mellitus / Delayed / Incidence not known
peripheral edema / Delayed / Incidence not known
edema / Delayed / Incidence not known
decreased HDL cholesterol (HDL-C) concentration / Delayed / Incidence not known
vitamin B12 deficiency / Delayed / Incidence not known

abdominal pain / Early / 4.6-4.6
back pain / Delayed / 3.4-3.4
headache / Early / 3.2-3.2
diarrhea / Early / 2.3-2.3
nausea / Early / 2.3-2.3
rhinitis / Early / 2.3-2.3
asthenia / Delayed / 2.1-2.1
rash / Early / 1.4-1.4
urticaria / Rapid / 1.1-1.1
dyspepsia / Early / Incidence not known
appetite stimulation / Delayed / Incidence not known
flatulence / Early / Incidence not known
xerostomia / Early / Incidence not known
vomiting / Early / Incidence not known
eructation / Early / Incidence not known
anorexia / Delayed / Incidence not known
diaphoresis / Early / Incidence not known
maculopapular rash / Early / Incidence not known
fever / Early / Incidence not known
acne vulgaris / Delayed / Incidence not known
photosensitivity / Delayed / Incidence not known
skin irritation / Early / Incidence not known
pruritus / Rapid / Incidence not known
alopecia / Delayed / Incidence not known
musculoskeletal pain / Early / Incidence not known
weakness / Early / Incidence not known
muscle cramps / Delayed / Incidence not known
myalgia / Early / Incidence not known
arthralgia / Delayed / Incidence not known
malaise / Early / Incidence not known
ecchymosis / Delayed / Incidence not known
drowsiness / Early / Incidence not known
libido decrease / Delayed / Incidence not known
vertigo / Early / Incidence not known
anxiety / Delayed / Incidence not known
dizziness / Early / Incidence not known
paresthesias / Delayed / Incidence not known
insomnia / Early / Incidence not known
pharyngitis / Delayed / Incidence not known
cough / Delayed / Incidence not known
laryngitis / Delayed / Incidence not known
sinusitis / Delayed / Incidence not known
infection / Delayed / Incidence not known
gynecomastia / Delayed / Incidence not known
increased urinary frequency / Early / Incidence not known
weight loss / Delayed / Incidence not known
weight gain / Delayed / Incidence not known

Antara, Fenoglide, Lipofen, Lofibra, Tricor, Triglide

Rx

Fibrate antilipemic; prodrug hydrolyzed to fenofibroic acid
Used primarily for hypertriglyceridemia; also for primary hypercholesterolemia or mixed dyslipidemia
HMG-CoA reductase inhibitors more effective for hypercholesterolemia

Initially, 50—150 mg PO once daily, administered with a meal. Evaluate lipid serum concentrations at 4—8 week intervals. Maximum dosage is 150 mg PO once daily. Consider dosage reduction if serum lipid concentrations fall significantly below target goals.

Initially, 48—145 mg PO once daily, administered without regard to meals. Evaluate lipid serum concentrations at 4—8 week intervals. Maximum dosage is 145 mg/day PO. Consider dosage reduction if serum lipid concentrations fall significantly below target goals.

Initially, 50—160 mg PO once daily, administered without regard to meals. Evaluate lipid serum concentrations at 4—8 week intervals. Maximum dosage is 160 mg/day PO. Consider dosage reduction if serum lipid concentrations fall significantly below target goals.

Initially, 30—90 mg PO once daily, administered without regard to meals. Evaluate lipid serum concentrations at 4—8 week intervals. Maximum dosage is 90 mg PO once daily. Consider dosage reduction if serum lipid concentrations fall significantly below target goals.

Initially, 67—200 mg PO once daily, administered with a meal. Evaluate lipid serum concentrations at 4—8 week intervals. Maximum dosage is 200 mg PO once daily. Consider dosage reduction if serum lipid concentrations fall significantly below target goals.

Initially, 67 mg PO once daily, administered with a meal. If needed, adjust dosage up to 200 mg PO once daily. Evaluate lipid serum concentrations periodically during initial therapy. Consider dosage reduction if serum lipid concentrations fall significantly below target goals. Withdraw therapy in patients who do not have an adequate response after two months of treatment with the maximum recommended dose of 200 mg/day.

Initially, 54—160 mg PO once daily, administered with a meal. Evaluate lipid serum concentrations at 4—8 week intervals. Maximum dosage is 160 mg PO once daily. Consider dosage reduction if serum lipid concentrations fall significantly below target goals.

Initially, 54 mg PO once daily, administered with a meal. If needed, adjust dosage up to 160 mg PO once daily. Evaluate lipid serum concentrations periodically during initial therapy. Consider dosage reduction if serum lipid concentrations fall significantly below target goals. Withdraw therapy in patients who do not have an adequate response after two months of treatment with the maximum recommended dose of 160 mg/day.

Initially, 40—120 mg PO once daily, administered with a meal. Evaluate lipid serum concentrations at 4—8 week intervals. Maximum dosage is 120 mg PO once daily. Consider dosage reduction if serum lipid concentrations fall significantly below target goals.

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.

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.

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.

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.

67 mg PO once daily, initially. Monitor lipid concentrations periodically and adjust dose if needed; consider reducing dose if lipid concentrations fall significantly below target range. Max: 200 mg/day. Discontinue therapy in patients who do not have a satisfactory response after 2 months with 200 mg/day.

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.

54 mg PO once daily, initially. Monitor lipid concentrations periodically and adjust dose if needed; consider reducing dose if lipid concentrations fall significantly below target range. Max: 160 mg/day. Discontinue therapy in patients who do not have a satisfactory response after 2 months with 160 mg/day.

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.

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.

Fenofibrate is contraindicated in patients with hepatic dysfunction, including primary biliary cirrhosis, and in patients with an unexplained persistent liver function abnormality.

CrCl >= 80 mL/min: No dose adjustment is necessary.
CrCl 30—80 mL/min: Initially, 48 mg PO once daily for Tricor, 50 mg PO once daily for Triglide or Lipofen formulations, 30 mg PO once daily for Antara capsules, 40 mg once daily for Fenoglide, 54 mg PO once daily for Lofibra tablets, or 67 mg PO once daily for Lofibra capsules. Do not increase dosage until the effects of the initial dosage on renal function and serum lipid concentrations have been fully evaluated.
CrCl <=30 mL/min: Contraindicated.
 
 
Intermittent hemodialysis
Not applicable; fenofibrate is not recommended in patients with severe renal dysfunction. Fenofibrate is not removed during intermittent hemodialysis.

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; 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.
Alogliptin; 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.
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.
Atorvastatin; 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. (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.
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.
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 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 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 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 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.
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.
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.
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 Degludec; 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.
Insulin Glargine; 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.
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.
Linagliptin; 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.
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; 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. (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 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 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.
Niacin; 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.
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.
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.
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.
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.
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.

Antara/Fenofibrate/Fenofibrate, Micronized/Lipofen/Lofibra/Tricor Oral Cap: 30mg, 43mg, 50mg, 67mg, 90mg, 130mg, 134mg, 150mg, 200mg
Fenofibrate/Fenoglide/Lofibra/Tricor/Triglide Oral Tab: 40mg, 48mg, 54mg, 120mg, 145mg, 160mg

145 mg/day PO for Tricor tablets (new formulation); 160 mg/day PO for Triglide tablets; 200 mg/day for Lofibra capsules; 90 mg/day for Antara capsules; 150 mg/day PO for Lipofen capsules.

145 mg/day PO for Tricor tablets (new formulation); 160 mg/day PO for Triglide tablets; 200 mg/day for Lofibra capsules; 90 mg/day for Antara capsules; 150 mg/day PO for Lipofen capsules.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Many of the lipid-modifications of fenofibrate are thought to be mediated by activation of peroxisome proliferator activated receptors (PPARs). PPARs function to alter the transciption of genes involved in lipoprotein metabolism, especially those for apolipoproteins. Modulation of apolipoproteins alters the binding of lipoproteins to cellular receptors and the interaction of lipoproteins with enzymes. The pharmacologic results are complex.
 
Fenofibrate induces lipoprotein lipase and decreases hepatic production of apolipoprotein CIII via PPAR activity, which enhances plasma catabolism and clearance of triglyceride-rich particles. Fatty acid oxidation is enhanced by fenofibrate activation of acyl CoA synthetase and other enzymes. Inhibition of acetyl-CoA carboxylase and fatty acid synthetase activity by fenofibrate further decreases synthesis of triglycerides. The result is a marked reduction in plasma triglyceride and VLDL levels.
 
Fenofibrate appears to produce favorable changes in LDL, HDL, and total cholesterol. Fenofibrate appears to favorably affect LDL subfraction ratios. Fenofibrate increases the production of larger and less dense LDL fractions, which appears to promote LDL metabolism via the nonatherogenic receptor pathways. Small, dense LDL particles, which have been associated with atherosclerosis, are reduced in comparison. Lipoprotein a (LPa), a variant form of LDL, is also reduced by fenofibrate. Net LDL levels are usually reduced or unchanged. The greatest LDL reductions occur in patients with type IIa or IIb dyslipidemias. Fenofibrate appears to increase HDL cholesterol via increased transcription of genes for apolipoproteins AI and AII by PPAR, and via decreased activity of cholesteryl ester transfer protein. Fenofibrate may also decrease cholesterol synthesis and may increase the mobilization of cholesterol from arterial and peripheral tissues. Xanthomas and xanthelasmas have regressed during treatment with fenofibrate. There is some preliminary evidence of regression of atherosclerosis. Like other fibrates, fenofibrate causes a relative rise in the proportion of cholesterol to bile acids in the bile.
 
Fenofibrate has other pharmacologic effects that may have positive benefits in patients with hyperlipoproteinemia. Fenofibrate reduces serum fibrinogen, an independent risk factor for thrombosis. Fenofibrate also increases the urinary excretion of uric acid, which is debated as a cardiac risk factor in patients with type IV hyperlipoproteinemia.

Fenofibrate is administered orally. It is a prodrug that is rapidly and completely hydrolyzed by plasma esterases to fenofibric acid following oral administration. Fenofibrate is highly (more than 99%) protein-bound, primarily to albumin. Fenofibric acid is primarily conjugated with glucuronic acid. Approximately 60% of a dose is excreted in the urine, and 25% excreted in the feces. The elimination half-life of fenofibrate is 20 hours in patients with normal renal function.
 
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.[29393]

Peak concentrations of fenofibric acid generally occur within 4 to 6 hours of oral fenofibrate administration.
Fenofibrate micronized capsules (Lofibra formulation): Absorption is increased by approximately 35% under fed as compared to fasting conditions. This formulation is 30% more bioavailable than a non-micronized preparation that was never marketed in the US; based on blood levels, 67 mg of micronized fenofibrate is equivalent to 100 mg of the non-micronized formulation. Administer this formulation with a meal.
Fenofibrate micronized capsules (Antara formulation): 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 to 130 mg under fasting conditions. Extent of absorption is unaffected when Antara is 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 can be taken without regard to meals.[45781]
Fenofibrate 54 and 160 mg tablets (original Tricor tablet formulation): This formulation has increased bioavailability relative to the capsule formulation. Plasma concentrations following administration of the 54 and 160 mg tablets are equivalent under fed conditions to the 67 and 200 mg capsules, respectively. Bioavailability of the 54 and 160 mg tablets is further enhanced by administration with food. NOTE: Tricor 54 and 160 mg tablets are not currently available. In May 2005, generic equivalents were approved by the FDA.
Fenofibrate 48 and 145 mg tablets (new Tricor tablet formulation): The AUC and Cmax of fenofibrate 145 mg are not significantly different when administered under fasting versus nonfasting conditions. Plasma concentrations after administration of three 48 mg or one 145 mg tablets are equivalent under fed conditions to one 200 mg capsule. This formulation (approved November 2004) can be administered without regard to meals.
Fenofibrate 50 and 160 mg tablets (Triglide tablet formulation): In a single-dose pharmacokinetics study in healthy volunteers, the 160 mg tablet has been shown to have comparable bioavailability to a single dose of 200 mg fenofibrate micronized capsule. However, the 160 mg tablet exhibits a 32% higher rate of absorption compared to the 200 mg micronized capsule under low-fat fed conditions. The extent of absorption of Triglide is comparable between fed and fasted conditions; however, food increases the rate of absorption by approximately 55%. According to the manufacturer, this dosage formulation may be taken without regard to meals.
Fenofibrate 50 and 150 mg capsules (Lipofen formulation): The extent and rate of absorption after administration of 150 mg Lipofen capsules are equivalent under low-fat and high-fat fed conditions to 160 mg Tricor tablets. Administer this formulation with a meal.

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 occurred at higher doses in the presence of maternal toxicity.[29393]

Fenofibrate is contraindicated in breast-feeding women. Advise women to not breast-feed during fenofibrate treatment and for 5 days after the final dose because of the potential for serious adverse reactions in breast-fed 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 breast-fed infant, or the effects on milk production. Fenofibrate is present in the milk of rats.[29393] If pharmacotherapy is necessary for the nursing mother, 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 mother and her nursing infant.[30812]