Fenofibrate

Drug overview for FENOFIBRATE (fenofibrate):

Generic name: FENOFIBRATE (fen-oh-FYE-brate)
Drug class: Fibric Acid Derivatives
Therapeutic class: Cardiovascular Therapy Agents

Fenofibrate and fenofibric acid are fibric acid-derivative antilipemic agents. Fenofibric acid is the pharmacologically active moiety of fenofibrate.

No enhanced Uses information available for this drug.

DRUG IMAGES

FENOFIBRATE 54 MG TABLET
FENOFIBRATE 160 MG TABLET
FENOFIBRATE 200 MG CAPSULE
FENOFIBRATE 134 MG CAPSULE
FENOFIBRATE 67 MG CAPSULE

The following indications for FENOFIBRATE (fenofibrate) have been approved by the FDA:

Indications:
Hyperlipidemia
Hypertriglyceridemia

Professional Synonyms:
Abnormally increased triglycerides in the blood
Elevated triglyceride level
Hyperlipoidemia
Increased triglyceride levels
Lipemia
Lipidemia
Lipoidemia

Dosing information for FENOFIBRATE
DRUG LABEL	DOSING TYPE	DOSING INSTRUCTIONS
FENOFIBRATE 67 MG CAPSULE	Maintenance	Adults take 1 capsule (67 mg) by oral route once daily with food
FENOFIBRATE 134 MG CAPSULE	Maintenance	Adults take 1 capsule (134 mg) by oral route once daily with food
FENOFIBRATE 200 MG CAPSULE	Maintenance	Adults take 1 capsule (200 mg) by oral route once daily with food
FENOFIBRATE 54 MG TABLET	Maintenance	Adults take 1 tablet (54 mg) by oral route once daily
FENOFIBRATE 160 MG TABLET	Maintenance	Adults take 1 tablet (160 mg) by oral route once daily

Generic dosing information for FENOFIBRATE
DRUG LABEL	DOSING TYPE	DOSING INSTRUCTIONS
FENOFIBRATE 54 MG TABLET	Maintenance	Adults take 1 tablet (54 mg) by oral route once daily
FENOFIBRATE 160 MG TABLET	Maintenance	Adults take 1 tablet (160 mg) by oral route once daily
FENOFIBRATE 200 MG CAPSULE	Maintenance	Adults take 1 capsule (200 mg) by oral route once daily with food
FENOFIBRATE 134 MG CAPSULE	Maintenance	Adults take 1 capsule (134 mg) by oral route once daily with food
FENOFIBRATE 67 MG CAPSULE	Maintenance	Adults take 1 capsule (67 mg) by oral route once daily with food

The following drug interaction information is available for FENOFIBRATE (fenofibrate):

Contraindicated
Severe
Moderate

There are 0 contraindications.

There are 1 severe interactions. These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.

Drug Interaction	Drug Names
Selected Anticoagulants (Vit K antagonists)/Fibrates SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The exact mechanism is unknown. Fibric acid derivatives may displace anticoagulants from their plasma protein binding sites or may affect anticoagulant receptor sites. It has also been suggested that the effect may be related to the hypolipidemic action of the fibric acid derivatives. CLINICAL EFFECTS: Concurrent use of selected anticoagulants and fibric acid derivatives may increase the risk for bleeding. PREDISPOSING FACTORS: Severe hyperlipidemia, larger doses of the fibric acid derivative, and older age may predispose patients to this interaction. The risk for bleeding episodes may also be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: Patients receiving concurrent therapy with selected anticoagulants and a fibric acid derivative should be closely monitored for excessive anticoagulant effects. The dose of the anticoagulant may need to be adjusted if the fibric acid derivative is added to or discontinued from stabilized anticoagulant therapy. The time of highest risk for an anticoagulant drug interaction is when the precipitant drug is initiated or discontinued. When concurrent therapy is warranted, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin and/or hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. Discontinue anticoagulation in patients with active pathologic bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. Contact the prescriber before initiating, altering the dose or discontinuing either drug. DISCUSSION: There have been case reports of bezafibrate,(1) clofibrate, (2-5) fenofibrate,(6-8) and gemfibrozil(9-11) interacting with warfarin. The interactions between clofibrate(12-14) and and warfarin and gemfibrozil(15) and warfarin have also been documented in clinical trials. There are also case reports of bezafibrate(16) and clofibrate(17) interacting with dicumarol. A study showed that bezafibrate increased the effects of phenprocoumon.(18)	ANISINDIONE, DICUMAROL, JANTOVEN, PHENINDIONE, WARFARIN SODIUM

Drug Interaction

Drug Names

Selected Anticoagulants (Vit K antagonists)/Fibrates

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: The exact mechanism is unknown. Fibric acid derivatives may displace anticoagulants from their plasma protein binding sites or may affect anticoagulant receptor sites. It has also been suggested that the effect may be related to the hypolipidemic action of the fibric acid derivatives.

CLINICAL EFFECTS: Concurrent use of selected anticoagulants and fibric acid derivatives may increase the risk for bleeding.

PREDISPOSING FACTORS: Severe hyperlipidemia, larger doses of the fibric acid derivative, and older age may predispose patients to this interaction. The risk for bleeding episodes may also be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs).

PATIENT MANAGEMENT: Patients receiving concurrent therapy with selected anticoagulants and a fibric acid derivative should be closely monitored for excessive anticoagulant effects. The dose of the anticoagulant may need to be adjusted if the fibric acid derivative is added to or discontinued from stabilized anticoagulant therapy. The time of highest risk for an anticoagulant drug interaction is when the precipitant drug is initiated or discontinued.

When concurrent therapy is warranted, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin and/or hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. Discontinue anticoagulation in patients with active pathologic bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. Contact the prescriber before initiating, altering the dose or discontinuing either drug.

DISCUSSION: There have been case reports of bezafibrate,(1) clofibrate, (2-5) fenofibrate,(6-8) and gemfibrozil(9-11) interacting with warfarin. The interactions between clofibrate(12-14) and and warfarin and gemfibrozil(15) and warfarin have also been documented in clinical trials. There are also case reports of bezafibrate(16) and clofibrate(17) interacting with dicumarol. A study showed that bezafibrate increased the effects of phenprocoumon.(18)

ANISINDIONE, DICUMAROL, JANTOVEN, PHENINDIONE, WARFARIN SODIUM

There are 6 moderate interactions. The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.

Drug Interaction	Drug Names
Ezetimibe/Fibrates SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Both ezetimibe and fibrates may increase cholesterol excretion in the bile. Fibrates may inhibit the metabolism of ezetimibe.(1) CLINICAL EFFECTS: Concurrent administration of ezetimibe may result in cholelithiasis, elevated levels of ezetimibe, and toxicity.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of ezetimibe states that the concurrent use of ezetimibe and fibrates other than fenofibrate is not recommended.(1) The Australian manufacturer of ezetimibe states that concurrent use with fenofibrate in patients with gall bladder disease is contraindicated.(2) Patients receiving concurrent therapy with any fibrate should be monitored for cholelithiasis and increased ezetimibe side effects. If cholelithiasis is suspected, gallbladder studies are indicated and alternative therapy may need to be utilized.(1) DISCUSSION: Fibrates have been shown to increase cholesterol excretion into the bile, leading to cholelithiasis. Ezetimibe has been shown in dogs to increase cholesterol in the gallbladder bile.(1) In a study in 32 subjects, concurrent fenofibrate and ezetimibe increased the maximum concentration (Cmax) and area-under-curve (AUC) of total ezetimibe by 64% and 48%, respectively. There was no significant effect on fenofibrate pharmacokinetics. Concomitant fenofibrate increased total ezetimibe concentrations by 1.5-fold.(1) In a study in 625 patients for up to 12 weeks and 576 patients for up to an additional 48 weeks, concurrent ezetimibe and fenofibrate was effective at lowering total cholesterol, LDL-C, Apo B, and non-HDL-C. The number of patients was inadequate to assess gallbladder risk; however, 0.6% of patients in the fenofibrate monotherapy group experienced cholecystectomy versus 1.7% during concurrent therapy.(1) In a study in 12 healthy subjects, concurrent gemfibrozil and ezetimibe increased the bioavailability of ezetimibe by 1.7-fold. There was no significant effect on gemfibrozil pharmacokinetics.(1)	EZETIMIBE, EZETIMIBE-SIMVASTATIN, NEXLIZET, ROSUVASTATIN-EZETIMIBE, ROSZET, VYTORIN, ZETIA
Fenofibrate; Gemfibrozil/Bile Acid Sequestrants SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Bile acid sequestrants may bind to fenofibrate and gemfibrozil resulting in decreased absorption of fenofibrate and gemfibrozil.(1,2) CLINICAL EFFECTS: Concurrent use of fenofibrate and gemfibrozil with bile acid sequestrants may result in decreased fenofibrate absorption and clinical effects.(1,2) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer states that fenofibrate should be administered 1 hour before or 4-6 hours after administration of bile acid sequestrants.(1) The US manufacturer states that gemfibrozil should be administered 2 hours apart from bile acid sequestrants.(2) DISCUSSION: Bile acid sequestrants are known to bind to drugs when given concurrently. Administration with fenofibrate and gemfibrozil may result in decreased systemic absorption.(1,2)	CHOLESTYRAMINE, CHOLESTYRAMINE LIGHT, CHOLESTYRAMINE RESIN, COLESEVELAM HCL, COLESTID, COLESTIPOL HCL, PREVALITE, QUESTRAN, QUESTRAN LIGHT, WELCHOL
Colchicine/Fibrates SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The exact mechanism of action is not clear. Concurrent use of colchicine and fibrates may result in additive or synergistic risk for myopathy or rhabdomyolysis.(1-2) CLINICAL EFFECTS: Concurrent use of colchicine and fibrates have been associated with myopathy and rhabdomyolysis.(1-2) PREDISPOSING FACTORS: This interaction is expected to be more severe in the elderly and in patients with renal impairment.(1-3) PATIENT MANAGEMENT: The risks and benefits of colchicine should be carefully weighed in patients who are currently taking fibrates. Assure that colchicine dosage has been reduced in patients with a creatinine clearance < 30 mL/min. Patients should be monitored and instructed to report any signs or symptoms of unexpected muscle pain, tenderness or weakness.(1) DISCUSSION: Neuromyopathy was reported in a patient maintained on bezafibrate who received colchicine for recurrent gout.(4) Rhabdomyolysis was reported in a patient following the addition of gemfibrozil to colchicine therapy. The patient had pre-existing mild renal failure, hepatitis B-related chronic liver disease, and amyloidosis, which may have contributed.(3)	COLCHICINE, COLCRYS, GLOPERBA, LODOCO, MITIGARE, PROBENECID-COLCHICINE
Selected HMG-CoA Reductase Inhibitors/Fenofibrate SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Unknown. CLINICAL EFFECTS: Concurrent administration of HMG-CoA reductase inhibitors and fibric acid derivatives has been associated with severe myopathy, rhabdomyolysis and acute renal failure. PREDISPOSING FACTORS: The risk for myopathy or rhabdomyolysis may be greater in patients 65 years and older, inadequately treated hypothyroidism, renal impairment, carnitine deficiency, malignant hyperthermia, or in patients with a history of myopathy or rhabdomyolysis. Patients with a SLCO1B1 polymorphism that leads to decreased function of the hepatic uptake transporter OATP1B1 may have increased statin concentrations and be predisposed to myopathy or rhabdomyolysis. Patients on fluvastatin who are CYP2C9 intermediate or poor metabolizers may have increased fluvastatin concentrations and risk of myopathy. Patients on rosuvastatin with ABCG2 polymorphisms leading to decreased or poor BCRP transporter function may have increased rosuvastatin concentrations and risk of myopathy. PATIENT MANAGEMENT: When possible, avoid administration of these drugs concomitantly unless patients require aggressive therapy. Instruct patients to report any unexplained muscle pain, tenderness or weakness. If muscular symptoms develop, monitor serum creatine kinase levels and renal function. One or both agents may need to be discontinued. The American College of Cardiology and American Heart Association Guidelines state that fenofibrate may be considered concomitantly with a low- or moderate-intensity statin only if the benefits from atherosclerotic cardiovascular risk reduction or triglyceride lowering when triglycerides are greater than or equal to 500 mg/dL are judged to outweigh the potential risk for adverse effects.(20) The European Society of Cardiology and European Atherosclerosis Society recommend concomitant statin-fenofibrate therapy in patients with atherogenic combined dyslipidemia, especially patients with metabolic syndrome and/or diabetes.(21) The US manufacturer of fenofibrate states that concurrent therapy with HMG CO-A reductase inhibitors should be avoided unless the benefit of further decreases in lipid levels is likely to outweigh the increased risk. Fenofibrate may be preferred over gemfibrozil in patients who do require concurrent statin and fibrate therapy.(9) The manufacturer of pravastatin states that concurrent therapy should be avoided unless the benefits of combination therapy outweigh the risks.(6) The Canadian manufacturer of rosuvastatin states that concurrent therapy with other fibrates should be approached with caution. The Australian and UK manufacturers of rosuvastatin state that rosuvastatin 40 mg is contraindicated with concomitant use of fibrates.(27,28) The risks of concurrent use of fibrates should be carefully weighed against the benefits. Patients taking a fibrate should start rosuvastatin therapy with the 5 mg dose. The US manufacturer of rosuvastatin states that the concurrent use of fenofibrate should be carefully weighed against the benefits. In patients receiving concurrent fenofibrate, a dosage reduction of rosuvastatin should be considered.(5) The manufacturer of simvastatin states that concurrent therapy with other fibrates should be approached with caution.(7) DISCUSSION: Concurrent fenofibrate (160 mg daily) increased the AUC and Cmax of pitavastatin (4 mg daily) by 18% and 11%, respectively. Concurrent fenofibrate (145 mg) with pravastatin (40 mg) increased pravastatin Cmax and AUC by 36% (range from 69% decrease to 321% increase) and 28% (range from 54% decrease to 128% increase), respectively, and the 3-alpha-hydroxy-iso-pravastatin Cmax and AUC by 55% (range from 32% decrease to 314% increase) and by 39% (range from 24% decrease to 261% increase), respectively. A single dose of pravastatin had no effect on the kinetics of fenofibrate. In a study in 24 healthy subjects, concurrent fenofibrate (160 mg daily) increased the average AUC of pravastatin (40 mg daily) by 19-28%; however, individual changes were variable and not statistically significant. Concurrent fenofibrate and rosuvastatin resulted in no significant changes in rosuvastatin or fenofibrate levels; however, rhabdomyolysis has been reported during concurrent therapy. Concurrent fenofibrate and simvastatin resulted in no significant changes in simvastatin or fenofibrate levels; however, rhabdomyolysis has been reported during concurrent therapy. In a study in 29 patients, 4 patients reported myalgia during concurrent simvastatin and fenofibrate, compared with no reports during concurrent simvastatin and cholestyramine. The risk of rhabdomyolysis with concurrent fibrate and HMG CoA reductase inhibitor therapy appears to be greater with gemfibrozil. Analysis of the FDA Adverse Event Report database indicates that the rate is 30 times higher with gemfibrozil than with fenofibrate. In an analysis of data from the Veteran's Administration over a 2 year period, there were 149 reports of rhabdomyolysis in 93,677 (0.016%) patients receiving concurrent gemfibrozil and statin therapy compared with no reports in 1,830 patients receiving concurrent fenofibrate and statin therapy. In a study in 66 healthy volunteers, concomitant administration of fenofibrate (160 mg for 7 days) and atorvastatin (40 mg single dose) did not result in a clinically significant change in the atorvastatin AUC.(22) A meta-analysis of 6 randomized controlled trials (including approximately 1600 patients) found no cases of myopathy or rhabdomyolysis in combination therapy of fenofibrate with simvastatin, fluvastatin, or atorvastatin. A comparison of the incidence of creatine kinase greater than 5 times the ULN between combination statin-fenofibrate and statin monotherapy was found to be not significant.(23) A meta-analysis of 13 randomized controlled trials (including approximately 7000 patients) found no significant difference in the incidence of elevated creatine kinase or muscle-associated adverse effects between single-drug statin therapy or combination fenofibrate-statin therapy.(24) The ACCORD trial showed that fenofibrate-simvastatin concomitant therapy had similar rates as simvastatin alone for myopathy, myositis, or rhabdomyolysis.(25) The ACCORD trial was a randomized trial of 5518 patients with type 2 diabetes receiving simvastatin (40 mg per day or less) and either fenofibrate (initial dose of 160 mg per day, dose adjusted for renal function) or placebo. At the mean follow up of 4.7 years, the primary efficacy endpoint of first occurrence of a major cardiovascular event, including nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes, occurred at an annual rate of 2.2% in the fenofibrate group and 2.4 % in the placebo group (p=0.32).(26) Selected HMG-CoA reductase inhibitors linked to this monograph include: fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin.	ALTOPREV, CRESTOR, EZALLOR SPRINKLE, EZETIMIBE-SIMVASTATIN, FLOLIPID, FLUVASTATIN ER, FLUVASTATIN SODIUM, LESCOL XL, LIVALO, LOVASTATIN, PITAVASTATIN CALCIUM, PRAVASTATIN SODIUM, ROSUVASTATIN CALCIUM, ROSUVASTATIN-EZETIMIBE, ROSZET, SIMVASTATIN, VYTORIN, ZOCOR, ZYPITAMAG
Atorvastatin/Fenofibrate SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Unknown. CLINICAL EFFECTS: Concurrent administration of atorvastatin and fibric acid derivatives has been associated with severe myopathy, rhabdomyolysis and acute renal failure. PREDISPOSING FACTORS: The risk for myopathy or rhabdomyolysis may be greater in patients 65 years and older, inadequately treated hypothyroidism, renal impairment, carnitine deficiency, malignant hyperthermia, or in patients with a history of myopathy or rhabdomyolysis. Patients with a SLCO1B1 polymorphism that leads to decreased function of the hepatic uptake transporter OATP1B1 may have increased statin concentrations and be predisposed to myopathy or rhabdomyolysis. PATIENT MANAGEMENT: When possible, avoid administration of atorvastatin and fibric acid derivatives concomitantly unless patients require aggressive therapy. Instruct patients to report any unexplained muscle pain, tenderness or weakness. If muscular symptoms develop, monitor serum creatine kinase levels and renal function. One or both agents may need to be discontinued. The American College of Cardiology and American Heart Association Guidelines state that fenofibrate may be considered concomitantly with a low- or moderate-intensity statin only if the benefits from atherosclerotic cardiovascular risk reduction or triglyceride lowering when triglycerides are greater than or equal to 500 mg/dL are judged to outweigh the potential risk for adverse effects.(20) The European Society of Cardiology and European Atherosclerosis Society recommend concomitant statin-fenofibrate therapy in patients with atherogenic combined dyslipidemia, especially patients with metabolic syndrome and/or diabetes.(21) The US manufacturer of fenofibrate states that concurrent therapy with HMG CO-A reductase inhibitors should be avoided unless the benefit of further decreases in lipid levels is likely to outweigh the increased risk. Fenofibrate may be preferred over gemfibrozil in patients who do require concurrent statin and fibrate therapy.(9) DISCUSSION: Concurrent fenofibrate (145 mg) with atorvastatin (20 mg) decreased the atorvastatin area-under-curve (AUC) by 17% (range from 67% decrease to 44% increase). Atorvastatin maximum concentration (Cmax) and the kinetics of fenofibrate were not significantly affected. The risk of rhabdomyolysis with concurrent fibrate and HMG CoA reductase inhibitor therapy appears to be greater with gemfibrozil. Analysis of the FDA Adverse Event Report database indicates that the rate is 30 times higher with gemfibrozil than with fenofibrate. In an analysis of data from the Veteran's Administration over a 2 year period, there were 149 reports of rhabdomyolysis in 93,677 (0.016%) patients receiving concurrent gemfibrozil and statin therapy compared with no reports in 1,830 patients receiving concurrent fenofibrate and statin therapy. In a study in 66 healthy volunteers, concomitant administration of fenofibrate (160 mg for 7 days) and atorvastatin (40 mg single dose) did not result in a clinically significant change in the atorvastatin AUC.(22) A meta-analysis of 6 randomized controlled trials (including approximately 1600 patients) found no cases of myopathy or rhabdomyolysis in combination therapy of fenofibrate with simvastatin, fluvastatin, or atorvastatin. A comparison of the incidence of creatine kinase greater than 5 times the ULN between combination statin-fenofibrate and statin monotherapy was found to be not significant.(23) A meta-analysis of 13 randomized controlled trials (including approximately 7000 patients) found no significant difference in the incidence of elevated creatine kinase or muscle-associated adverse effects between single-drug statin therapy or combination fenofibrate-statin therapy.(24)	AMLODIPINE-ATORVASTATIN, ATORVALIQ, ATORVASTATIN CALCIUM, CADUET, LIPITOR
Cyclosporine/Selected Fibrates SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Concurrent use of cyclosporine and fibrates may result in additive nephrotoxicity.(1) CLINICAL EFFECTS: Concurrent use of cyclosporine and fibrates may result in additive nephrotoxicity.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Use concurrent cyclosporine and fibrates with caution. If concurrent use is warranted, use the lowest effective dose of the fibrate and monitor patients for decreased renal function. DISCUSSION: In a study in heart-transplant patients, concurrent fenofibrate had no effect on cyclosporine levels, but patients developed increased serum concentration.(2) Two studies in transplant patients found that gemfibrozil had no effect on cyclosporine levels or renal function.(3,4)	CYCLOSPORINE, CYCLOSPORINE MODIFIED, GENGRAF, NEORAL, SANDIMMUNE

The following contraindication information is available for FENOFIBRATE (fenofibrate):

Overview
Contraindicated
Severe
Moderate

Drug contraindication overview.

Fenofibrate and fenofibric acid are contraindicated in patients with severe renal impairment (including those undergoing dialysis), active liver disease (including primary biliary cirrhosis and unexplained and persistent liver function abnormality), or preexisting gallbladder disease. The drugs also are contraindicated in nursing women and in patients with known hypersensitivity to fenofibrate or fenofibric acid.

There are 7 contraindications. Absolute contraindication.

Contraindication List
Child-pugh class A hepatic impairment
Child-pugh class B hepatic impairment
Child-pugh class C hepatic impairment
Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
Chronic kidney disease stage 5 (failure) GFr<15 ml/min
Lactation
Primary biliary cholangitis

There are 9 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Acute pancreatitis
Chronic kidney disease stage 2 (mild) GFR 60-89 ml/min
Chronic kidney disease stage 3A (moderate) GFR 45-59 ml/min
Chronic kidney disease stage 3B (moderate) GFR 30-44 ml/min
Disease of liver
Gallbladder disease
Myopathy
Myositis
Rhabdomyolysis

There are 6 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Agranulocytosis
Anemia
Hypothyroidism
Kidney disease with likely reduction in glomerular filtration rate (GFr)
Leukopenia
Thrombocytopenic disorder

The following adverse reaction information is available for FENOFIBRATE (fenofibrate):

Overview
Severe
Less Severe

Adverse reaction overview.

Adverse effects occurring in 2% or more of patients receiving fenofibrate include abnormal liver function tests (e.g., increased ALT and/or AST), respiratory disorder, abdominal pain, back pain, headache, increased CK concentrations, diarrhea, nausea, rhinitis, constipation, asthenia, and flu syndrome. Adverse effects occurring in 2% or more of patients receiving fenofibric acid include abnormal liver function tests, including increased AST/ALT; increased CPK; and rhinitis.

There are 36 severe adverse reactions.

More Frequent	Less Frequent
Abnormal hepatic function tests Increased alanine transaminase Increased aspartate transaminase	Infection Myalgia Pruritus of skin Skin rash Thrombophlebitis Urticaria

Rare/Very Rare
Acute pancreatitis Acute renal failure Agranulocytosis Anaphylaxis Angioedema Biliary calculus Cholecystitis Cholestatic hepatitis DRESS syndrome Eczema Hepatic cirrhosis Hepatic failure Hepatitis Hepatocellular damage Hyperbilirubinemia Hypersensitivity pneumonitis Interstitial lung disease Jaundice Muscle weakness Myositis Pulmonary thromboembolism Respiration changes Rhabdomyolysis Stevens-johnson syndrome Thrombocytopenic disorder Toxic epidermal necrolysis Venous thrombosis

Rare/Very Rare

Acute pancreatitis
Acute renal failure
Agranulocytosis
Anaphylaxis
Angioedema
Biliary calculus
Cholecystitis
Cholestatic hepatitis
DRESS syndrome
Eczema
Hepatic cirrhosis
Hepatic failure
Hepatitis
Hepatocellular damage
Hyperbilirubinemia
Hypersensitivity pneumonitis
Interstitial lung disease
Jaundice
Muscle weakness
Myositis
Pulmonary thromboembolism
Respiration changes
Rhabdomyolysis
Stevens-johnson syndrome
Thrombocytopenic disorder
Toxic epidermal necrolysis
Venous thrombosis

There are 26 less severe adverse reactions.

More Frequent	Less Frequent
Rhinitis	Acute abdominal pain Back pain Constipation Dizziness Eructation Flatulence Flu-like symptoms General weakness Headache disorder Libido changes Myopathy Nausea Ocular irritation Pharyngitis Skin photosensitivity Upper respiratory infection

Rare/Very Rare
Anemia Arthralgia Cough Diarrhea Dyspepsia High density lipoprotein deficiency Increased creatine kinase level Insomnia Muscle spasm

The following precautions are available for FENOFIBRATE (fenofibrate):

Pediatric
Pregnant
Lactation
Geriatric

Safety and efficacy of fenofibrate and fenofibric acid have not been established in pediatric patients.

Contraindicated

None

Severe Precaution

None

Management or Monitoring Precaution

None

There are insufficient data in pregnant women to determine whether fenofibrate is associated with a risk of developmental adverse effects. In animal reproduction studies, no evidence of embryofetal toxicity was observed with dose exposures up to the maximum recommended clinical dose. Fenofibrate should be used during pregnancy only if the potential benefits justify the potential risks to the fetus.

Because of the potential for serious adverse effects in nursing infants, fenofibrate and fenofibric acid should not be used in nursing women; a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman. (See Cautions: Contraindications.)

Because fenofibric acid is substantially excreted by the kidneys, and geriatric patients are more likely to have decreased renal function, dosage of fenofibrate and fenofibric acid for geriatric patients should be selected based on renal function. (See Dosage and Administration: Special Populations.) Renal function monitoring should be considered in geriatric patients receiving fenofibrate or fenofibric acid therapy.

Hyperlipidemia
E78.2	Mixed hyperlipidemia
E78.4	Other hyperlipidemia
E78.49	Other hyperlipidemia
E78.5	Hyperlipidemia, unspecified
Hypertriglyceridemia
E78.1	Pure hyperglyceridemia
E78.2	Mixed hyperlipidemia