Choline fenofibrate

Choline fenofibrate
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Kiran Singh, M.D. [2]

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Overview

Choline fenofibrate is an antihyperlipedemic that is FDA approved for the treatment of primary hypercholesterolemia or mixed dyslipidemia and hypertriglyceridemia. Common adverse reactions include headache, back pain, nasopharyngitis, nausea, myalgia, diarrhea, and upper respiratory tract infection.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Indications

Coadministration Therapy with Statins for the Treatment of Mixed Dyslipidemia

• Fenofibric acid delayed-release capsules are indicated as an adjunct to diet in combination with a statin to reduce TG and increase HDL-C in patients with mixed dyslipidemia and CHD or a CHD risk equivalent who are on optimal statin therapy to achieve their LDL-C goal.

• CHD risk equivalents comprise:

• Other clinical forms of atherosclerotic disease (peripheral arterial disease, abdominal aortic aneurysm, and symptomatic carotid artery disease);

Diabetes;

• Multiple risk factors that confer a 10-year risk for CHD > 20%

Treatment of Severe Hypertriglyceridemia

• Fenofibric acid delayed-release capsules are indicated as adjunctive therapy to diet to reduce TG in patients with severe hypertriglyceridemia. Improving glycemic control in diabetic patients showing fasting chylomicronemia will usually obviate the need for pharmacological intervention. Markedly elevated levels of serum triglycerides (e.g. > 2,000 mg/dL) may increase the risk of developing pancreatitis. The effect of fenofibric acid delayed-release capsules therapy on reducing this risk has not been adequately studied.

Treatment of Primary Hypercholesterolemia or Mixed Dyslipidemia

• Fenofibric acid delayed-release capsules are indicated as adjunctive therapy to diet to reduce elevated low-density lipoprotein cholesterol (LDL-C), total cholesterol (Total-C), triglycerides (TG), and apolipoprotein B (Apo B), and to increase high-density lipoprotein cholesterol (HDL-C) in patients with primary hypercholesterolemia or mixed dyslipidemia.

Important Limitations of Use

• No incremental benefit of fenofibric acid delayed-release capsules on cardiovascular morbidity and mortality over and above that demonstrated for statin monotherapy has been established. Fenofibrate at a dose equivalent to 135 mg of fenofibric acid delayed-release capsules was not shown to reduce coronary heart disease morbidity and mortality in 2 large, randomized controlled trials of patients with type 2 diabetes mellitus.

General Considerations for Treatment

• Laboratory studies should be performed to establish that lipid levels are abnormal before instituting fenofibric acid delayed-release capsules therapy.

• Every reasonable attempt should be made to control serum lipids with non-drug methods including appropriate diet, exercise, weight loss in obese patients, and control of any medical problems such as diabetes mellitus and hypothyroidism that may be contributing to the lipid abnormalities. Medications known to exacerbate hypertriglyceridemia (beta-blockers, thiazides, estrogens) should be discontinued or changed if possible, and excessive alcohol intake should be addressed before triglyceride-lowering drug therapy is considered. If the decision is made to use lipid-altering drugs, the patient should be instructed that this does not reduce the importance of adhering to diet.

• Drug therapy is not indicated for patients who have elevations of chylomicrons and plasma triglycerides, but who have normal levels of VLDL.

Dosage

General Considerations

• Patients should be placed on an appropriate lipid-lowering diet before receiving Fenofibric Acid Delayed-Release Capsules as monotherapy or coadministered with a statin, and should continue this diet during treatment. Fenofibric acid delayed-release capsules can be taken without regard to meals. Patients should be advised to swallow fenofibric acid delayed-release capsules whole. Do not open, crush, dissolve, or chew capsules. Serum lipids should be monitored periodically.

Coadministration Therapy with Statins for the Treatment of Mixed Dyslipidemia

• Fenofibric acid delayed-release capsules 135 mg may be coadministered with an HMG-CoA reductase inhibitor (statin) in patients with mixed dyslipidemia. For convenience, the daily dose of fenofibric acid delayed-release capsules may be taken at the same time as a statin, according to the dosing recommendations for each medication. Coadministration with the maximum dose of a statin has not been evaluated in clinical studies and should be avoided unless the benefits are expected to outweigh the risks.

Severe Hypertriglyceridemia

• The initial dose of fenofibric acid delayed-release capsules is 45 to 135 mg once daily. Dosage should be individualized according to patient response, and should be adjusted if necessary following repeat lipid determinations at 4 to 8 week intervals. The maximum dose is 135 mg once daily.

Primary Hypercholesterolemia or Mixed Dyslipidemia

• The dose of fenofibric acid delayed-release capsules is 135 mg once daily.

Impaired Renal Function

• Treatment with fenofibric acid delayed-release capsules should be initiated at a dose of 45 mg once daily in patients with mild to moderate renal impairment and should only be increased after evaluation of the effects on renal function and lipid levels at this dose. The use of fenofibric acid delayed-release capsules should be avoided in patients with severely impaired renal function.

Geriatric Patients

• Dose selection for the elderly should be made on the basis of renal function.

DOSAGE FORMS AND STRENGTHS

• 45 mg fenofibric acid delayed-release capsules with a dark brown opaque cap and yellow opaque body imprinted with “Par” on the cap and “C209” on the body in black ink.
• 135 mg fenofibric acid delayed release capsules with a light blue opaque cap and yellow opaque body imprinted with “Par” on the cap and “C210” on the body in black ink.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

Condition1

• Developed by:

• Class of Recommendation:

There is limited information regarding Off-Label Guideline-Supported Use of Choline fenofibrate in adult patients.

Non–Guideline-Supported Use

• There is limited information regarding Off-Label Non–Guideline-Supported Use of Choline fenofibrate in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

• There is limited information regarding FDA-Labeled Use of Choline fenofibrate in pediatric patients.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

• There is limited information regarding Off-Label Guideline-Supported Use of Choline fenofibrate in pediatric patients.

Non–Guideline-Supported Use

• There is limited information regarding Off-Label Non–Guideline-Supported Use of Choline fenofibrate in pediatric patients.

Contraindications

Fenofibric acid delayed-release capsules are contraindicated in:

• Patients with severe renal impairment, including those receiving dialysis.

• Patients with active liver disease, including those with primary biliary cirrhosis and unexplained persistent liver function abnormalities.

• Patients with preexisting gallbladder disease.

• Nursing mothers.

• Patients with hypersensitivity to fenofibric acid or fenofibrate.

• When fenofibric acid delayed-release capsules are coadministered with a statin, refer to the Contraindications section of the respective statin labeling.

Warnings

Mortality and Coronary Heart Disease Morbidity

• The effect of fenofibric acid delayed-release capsules on coronary heart disease morbidity and mortality and non-cardiovascular mortality has not been established. Because of similarities between fenofibric acid delayed-release capsules and fenofibrate, clofibrate, and gemfibrozil, the findings in the following large randomized, placebo-controlled clinical studies with these fibrate drugs may also apply to fenofibric acid delayed-release capsules.

• The Action to Control Cardiovascular Risk in Diabetes Lipid (ACCORD Lipid) trial was a randomized placebo-controlled study of 5518 patients with type 2 diabetes mellitus on background statin therapy treated with fenofibrate. The mean duration of follow-up was 4.7 years. Fenofibrate plus statin combination therapy showed a non-significant 8% relative risk reduction in the primary outcome of major adverse cardiovascular events (MACE), a composite of non-fatal myocardial infarction, non-fatal stroke, and cardiovascular disease death (hazard ratio [HR] 0.92, 95% CI 0.79 to 1.08) (p=0.32) as compared to statin monotherapy. In a gender subgroup analysis, the hazard ratio for MACE in men receiving combination therapy versus statin monotherapy was 0.82 (95% CI 0.69 to 0.99), and the hazard ratio for MACE in women receiving combination therapy versus statin monotherapy was 1.38 (95% CI 0.98 to 1.94) (interaction p=0.01). The clinical significance of this subgroup finding is unclear.

• The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study was a 5-year randomized, placebo-controlled study of 9795 patients with type 2 diabetes mellitus treated with fenofibrate. Fenofibrate demonstrated a non-significant 11% relative reduction in the primary outcome of coronary heart disease events (hazard ratio [HR] 0.89, 95% CI 0.75 to 1.05, p = 0.16) and a significant 11% reduction in the secondary outcome of total cardiovascular disease events (HR 0.89 [0.80 to 0.99], p = 0.04). There was a non-significant 11% (HR 1.11 [0.95, 1.29], p = 0.18) and 19% (HR 1.19 [0.90, 1.57], p = 0.22) increase in total and coronary heart disease mortality, respectively, with fenofibrate as compared to placebo.

• In the Coronary Drug Project, a large study of post-myocardial infarction patients treated for 5 years with clofibrate, there was no difference in mortality seen between the clofibrate group and the placebo group. There was, however, a difference in the rate of cholelithiasis and cholecystitis requiring surgery between the two groups (3.0% vs. 1.8%).

• In a study conducted by the World Health Organization (WHO), 5000 subjects without known coronary artery disease were treated with placebo or clofibrate for 5 years and followed for an additional one year. There was a statistically significant, higher age-adjusted all-cause mortality in the clofibrate group compared with the placebo group (5.70% vs. 3.96%, p = < 0.01). Excess mortality was due to a 33% increase in non-cardiovascular causes, including malignancy, post-cholecystectomy complications, and pancreatitis. This appeared to confirm the higher risk of gallbladder disease seen in clofibrate-treated patients studied in the Coronary Drug Project.

• The Helsinki Heart Study was a large (N = 4081) study of middle-aged men without a history of coronary artery disease. Subjects received either placebo or gemfibrozil for 5 years, with a 3.5 year open extension afterward. Total mortality was numerically higher in the gemfibrozil randomization group but did not achieve statistical significance (p = 0.19, 95% confidence interval for relative risk G:P = 0.91 to 1.64). Although cancer deaths trended higher in the gemfibrozil group (p = 0.11), cancers (excluding basal cell carcinoma) were diagnosed with equal frequency in both study groups. Due to the limited size of the study, the relative risk of death from any cause was not shown to be different than that seen in the 9 year follow-up data from WHO study (RR = 1.29). A secondary prevention component of the Helsinki Heart Study enrolled middle-aged men excluded from the primary prevention study because of known or suspected coronary heart disease. Subjects received gemfibrozil or placebo for 5 years. Although cardiac deaths trended higher in the gemfibrozil group, this was not statistically significant (hazard ratio 2.2, 95% confidence interval: 0.94 to 5.05).

Skeletal Muscle

• Fibrate and statin monotherapy increase the risk of myositis or myopathy, and have been associated with rhabdomyolysis. Data from observational studies suggest that the risk for rhabdomyolysis is increased when fibrates are coadministered with a statin (with a numerically higher rate observed with gemfibrozil/statin combination use compared to fenofibrate/statin combination use). Refer to the respective statin labeling for important drug-drug interactions that increase statin levels and could increase this risk. The risk for serious muscle toxicity appears to be increased in elderly patients and in patients with diabetes, renal failure, or hypothyroidism.

• In phase 3 clinical trials with fenofibric acid delayed-release capsules, myalgia was reported in 3.3% of patients treated with fenofibric acid delayed-release capsules monotherapy and 3.1% to 3.5% of patients treated with fenofibric acid delayed-release capsules coadministered with statins compared to 4.7% to 6.1% of patients treated with statin monotherapy. Increases in creatine phosphokinase (CPK) to > 5 times upper limit of normal occurred in no patients treated with fenofibric acid delayed-release capsules monotherapy and 0.2% to 1.2% of patients treated with fenofibric acid delayed-release capsules coadministered with statins compared to 0.4% to 1.3% of patients treated with statin monotherapy.

• Myopathy should be considered in any patient with diffuse myalgias, muscle tenderness or weakness, and/or marked elevations of CPK levels. Patients should promptly report unexplained muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever. CPK levels should be assessed in patients reporting these symptoms, and fenofibric acid delayed-release capsules and statin therapy should be discontinued if markedly elevated CPK levels occur or myopathy or myositis is suspected or diagnosed.

• Cases of myopathy, including rhabdomyolysis, have been reported with fenofibrates coadministered with colchicine, and caution should be exercised when prescribing fenofibrate with colchicine.

Liver Function

• Fenofibric acid delayed-release capsules at a dose of 135 mg once daily administered as monotherapy or coadministered with low to moderate doses of statins has been associated with increases in serum transaminases [AST (SGOT) or ALT (SGPT)]. In a pooled analysis of three double-blind controlled studies of fenofibric acid delayed-release capsules administered as monotherapy or in combination with statins, increases to > 3 times the upper limit of normal on two consecutive occasions in ALT and AST occurred in 1.9% and 0.2%, respectively, of patients receiving fenofibric acid delayed-release capsules monotherapy and in 1.3% and 0.4%, respectively, of patients receiving fenofibric acid delayed-release capsules coadministered with statins. Increases to > 3 times the upper limit of normal in ALT and AST occurred in no patients receiving low- to moderate-dose statin monotherapy. Increases to > 3 times the upper limit of normal in ALT and AST occurred in 0.8% and 0.4%, respectively in patients receiving high-dose statin monotherapy. In a long-term study of fenofibric acid delayed-release capsules coadministered with statins for up to 52 weeks, increases of > 3 times the upper limit of normal on two consecutive occasions of ALT and AST occurred in 1.2% and 0.5% of patients, respectively. When transaminase determinations were followed either after discontinuation of treatment or during continued treatment, a return to normal limits was usually observed. Increases in ALT and/or AST were not accompanied by increases in bilirubin or clinically significant increases in alkaline phosphatase.

• In a pooled analysis of 10 placebo-controlled trials of fenofibrate, increases to > 3 times the upper limit of normal in ALT occurred in 5.3% of patients taking fenofibrate versus 1.1% of patients treated with placebo. The incidence of increases in transaminases observed with fenofibrate therapy may be dose related. In an 8- week dose-ranging study of fenofibrate in hypertriglyceridemia, the incidence of ALT or AST elevations ≥ 3 times the upper limit of normal was 13% in patients receiving dosages equivalent to 90 mg to 135 mg fenofibric acid delayed-release capsules once daily and was 0% in those receiving dosages equivalent to 45 mg fenofibric acid delayed-release capsules once daily or less, or placebo. Hepatocellular, chronic active, and cholestatic hepatitis observed with fenofibrate therapy have been reported after exposures of weeks to several years. In extremely rare cases, cirrhosis has been reported in association with chronic active hepatitis.

• Baseline and regular monitoring of liver function, including serum ALT (SGPT) should be performed for the duration of therapy with fenofibric acid delayed-release capsules, and therapy discontinued if enzyme levels persist above 3 times the upper limit of normal.

Serum Creatinine

• Reversible elevations in serum creatinine have been reported in patients receiving fenofibric acid delayed-release capsules as monotherapy or coadministered with statins as well as patients receiving fenofibrate. In the pooled analysis of three double- blind controlled studies of fenofibric acid delayed-release capsules administered as monotherapy or in combination with statins, increases in creatinine to > 2 mg/dL occurred in 0.8% of patients treated with fenofibric acid delayed-release capsules monotherapy and 1.1% to 1.3% of patients treated with fenofibric acid delayed-release capsules coadministered with statins compared to 0% to 0.4% of patients treated with statin monotherapy. Elevations in serum creatinine were generally stable over time with no evidence for continued increases in serum creatinine with long-term therapy and tended to return to baseline following discontinuation of treatment. The clinical significance of these observations is unknown. Monitoring renal function in patients with renal impairment taking fenofibric acid delayed-release capsules is suggested. Renal monitoring should be considered for patients at risk for renal insufficiency, such as the elderly and those with diabetes.

Cholelithiasis

• Fenofibric acid delayed-release capsules, like fenofibrate, clofibrate, and gemfibrozil, may increase cholesterol excretion into the bile, potentially leading to cholelithiasis. If cholelithiasis is suspected, gallbladder studies are indicated. Fenofibric acid delayed-release capsules therapy should be discontinued if gallstones are found.

Coumarin Anticoagulants

• Caution should be exercised when fenofibric acid delayed-release capsules is given in conjunction with oral coumarin anticoagulants. Fenofibric acid delayed-release capsules may potentiate the anticoagulant effects of these agents resulting in prolongation of the prothrombin time/International Normalized Ratio (PT/INR). Frequent monitoring of PT/INR and dose adjustment of the oral anticoagulant are recommended until the PT/INR has stabilized in order to prevent bleeding complications.

Pancreatitis

• Pancreatitis has been reported in patients taking drugs of the fibrate class, including fenofibric acid delayed-release capsules. This occurrence 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.

Hematological Changes

• Mild to moderate hemoglobin, hematocrit, and white blood cell decreases have been observed in patients following initiation of fenofibric acid delayed-release capsules and fenofibrate therapy. However, these levels stabilize during long-term administration. Thrombocytopenia and agranulocytosis have been reported in individuals treated with fenofibrates. Periodic monitoring of red and white blood cell counts are recommended during the first 12 months of fenofibric acid delayed-release capsules administration.

Hypersensitivity Reactions

• Acute hypersensitivity reactions such as Stevens-Johnson syndrome and toxic necrolysis requiring patient hospitalization and treatment with steroids have been reported in individuals treated with fenofibrates.

Venothromboembolic Disease

• In the FIELD trial, pulmonary embolus (PE) and deep vein thrombosis (DVT) were observed at higher rates in the fenofibrate- than the placebo-treated group. Of 9,795 patients enrolled in FIELD, there were 4,900 in the placebo group and 4,895 in the fenofibrate group. For DVT, there were 48 events (1%) in the placebo group and 67 (1%) in the fenofibrate group (p = 0.074); and for PE, there were 32 (0.7%) events in the placebo group and 53 (1%) in the fenofibrate group (p = 0.022).

• In the Coronary Drug Project, a higher proportion of the clofibrate group experienced definite or suspected fatal or nonfatal PE or thrombophlebitis than the placebo group (5.2% vs. 3.3% at five years; p < 0.01).

Paradoxical Decreases in HDL Cholesterol Levels

• There have been postmarketing and clinical trial reports of severe decreases in HDL cholesterol levels (as low as 2 mg/dL) occurring in diabetic and non-diabetic patients initiated on fibrate therapy. The decrease in HDL-C is mirrored by a decrease in apolipoprotein A1. This decrease has been reported to occur within 2 weeks to years after initiation of fibrate therapy. The HDL-C levels remain depressed until fibrate therapy has been withdrawn; the response to withdrawal of fibrate therapy is rapid and sustained. The clinical significance of this decrease in HDL-C is unknown. It is recommended that HDL-C levels be checked within the first few months after initiation of fibrate therapy. If a severely depressed HDL-C level is detected, fibrate therapy should be withdrawn, and the HDL-C level monitored until it has returned to baseline, and fibrate therapy should not be re-initiated.

Adverse Reactions

Clinical Trials Experience

• Because clinical studies are conducted under widely varying conditions, adverse event rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug.

• Fenofibric acid delayed-release capsules

Monotherapy

• Treatment-emergent adverse events reported in 3% or more of patients treated with fenofibric acid delayed-release capsules during the randomized controlled trials are listed in TABLE 1 below.

• Coadministration Therapy with Statins (Double-blind Controlled Trials)

• Treatment-emergent adverse events reported in 3% or more of patients treated with fenofibric acid delayed-release capsules coadministered with statins during the randomized controlled trials are listed in table1 below.

This image is provided by the National Library of Medicine.

• Coadministration Therapy with Statins (Long-Term Exposure for up to 64 Weeks)

• Patients successfully completing any one of the three double-blind, controlled studies were eligible to participate in a 52-week long-term extension study where they received fenofibric acid delayed-release capsules coadministered with the moderate dose statin. A total of 2201 patients received at least one dose of fenofibric acid delayed-release capsules coadministered with a statin in the double-blind controlled study or the long-term extension study for up to a total of 64 weeks of treatment. Additional treatment-emergent adverse events (not listed in TABLE 1 above) reported in 3% or more of patients receiving fenofibric acid delayed-release capsules coadministered with a statin in either the double-blind controlled studies or the long-term extension study are provided below.

Infections and Infestations

• Bronchitis, influenza, and urinary tract infection.

Investigations

• AST increased, blood CPK increased, and hepatic enzyme increased.

Musculoskeletal and Connective Tissue Disorders

• Musculoskeletal pain.

Psychiatric Disorders

• Insomnia.

Respiratory, Thoracic, and Mediastinal Disorders

• Cough and pharyngolaryngeal pain.

Vascular Disorders

• Hypertension.

Fenofibrate

• Fenofibric acid is the active metabolite of fenofibrate. Adverse events reported by 2% or more of patients treated with fenofibrate and greater than placebo during double-blind, placebo-controlled trials are listed in TABLE 2. Adverse events led to discontinuation of treatment in 5.0% of patients treated with fenofibrate and in 3.0% treated with placebo. Increases in liver tests were the most frequent events, causing discontinuation of fenofibrate treatment in 1.6% of patients in double-blind trials.

This image is provided by the National Library of Medicine.

Postmarketing Experience

• The following adverse events have been identified during postapproval use of fenofibrate: myalgia, rhabdomyolysis, pancreatitis, renal failure, muscle spasms, acute renal failure, hepatitis, cirrhosis, anemia, arthralgia, asthenia, and severely depressed HDL-cholesterol levels.

• Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Drug Interactions

Coumarin Anticoagulants

• Potentiation of coumarin-type anticoagulant effect has been observed with prolongation of the PT/INR.

• Caution should be exercised when oral coumarin anticoagulants are given in conjunction with fenofibric acid delayed-release capsules. The dosage of the anticoagulant should be reduced to maintain the PT/INR at the desired level to prevent bleeding complications. Frequent PT/INR determinations are advisable until it has been definitely determined that the PT/INR has stabilized.

Bile Acid Binding Resins

• Since bile acid binding resins may bind other drugs given concurrently, patients should take fenofibric acid delayed-release capsules at least 1 hour before or 4 to 6 hours after a bile acid resin to avoid impeding its absorption.

Immunosuppressants

• Immunosuppressants such as cyclosporine and tacrolimus can produce nephrotoxicity with decreases in creatinine clearance and rises in serum creatinine, and because renal excretion is the primary elimination route of drugs of the fibrate class including fenofibric acid delayed-release capsules, there is a risk that an interaction will lead to deterioration of renal function. The benefits and risks of using fenofibric acid delayed-release capsules with immunosuppressants and other potentially nephrotoxic agents should be carefully considered, and the lowest effective dose employed.

Colchicine

• Cases of myopathy, including rhabdomyolysis, have been reported with fenofibrates coadministered with colchicine, and caution should be exercised when prescribing fenofibrate with colchicine.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): Pregnancy Category: C

• The safety of fenofibric acid delayed-release capsules in pregnant women has not been established. There are no adequate and well controlled studies of fenofibric acid delayed-release capsules in pregnant women. Fenofibric acid delayed-release capsules should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

• When fenofibric acid delayed-release capsules are administered with a statin in a woman of childbearing potential, refer to pregnancy category and product labeling for the statin. All statins are contraindicated in pregnant women.

• In pregnant rats given oral dietary doses of 14, 127, and 361 mg/kg/day from gestation day 6 to 15 during the period of organogenesis, adverse developmental findings were not observed at 14 mg/kg/day (less than 1 times the maximum recommended human dose [MRHD], based on body surface area comparisons; mg/m2). At higher multiples of human doses evidence of maternal toxicity was observed.

• In pregnant rabbits given oral gavage doses of 15, 150, and 300 mg/kg/day from gestation day 6 to 18 during the period of organogenesis and allowed to deliver, aborted litters were observed at 150 mg/kg/day (10 times the MRHD, based on body surface area comparisons; mg/m2). No developmental findings were observed at 15 mg/kg/day (at less than 1 times the MRHD, based on body surface area comparisons; mg/m2).

• In pregnant rats given oral dietary doses of 15, 75, and 300 mg/kg/day from gestation day 15 through lactation day 21 (weaning), maternal toxicity was observed at less than 1 times the MRHD, based on body surface area comparisons; mg/m2.

Pregnancy Category (AUS):

• Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Choline fenofibrate in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Choline fenofibrate during labor and delivery.

Nursing Mothers

• Fenofibric acid delayed-release capsules should not be used in nursing mothers. A decision should be made whether to discontinue nursing or to discontinue the drug taking into account the importance of the drug to the mother.

Pediatric Use

• The safety and effectiveness of fenofibric acid delayed-release capsules monotherapy or coadministration with a statin in pediatric patients have not been established.

Geriatic Use

• Fenofibric acid delayed-release capsules are substantially excreted by the kidney as fenofibric acid and fenofibric acid glucuronide, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Fenofibric acid exposure is not influenced by age. Since elderly patients have a higher incidence of renal impairment, dose selection for the elderly should be made on the basis of renal function. Elderly patients with normal renal function should require no dose modifications. Consider monitoring renal function in elderly patients taking fenofibric acid delayed-release capsules.

Gender

There is no FDA guidance on the use of Choline fenofibrate with respect to specific gender populations.

Race

There is no FDA guidance on the use of Choline fenofibrate with respect to specific racial populations.

Renal Impairment

• The use of fenofibric acid delayed-release capsules should be avoided in patients who have severe renal impairment. Dose reduction is required in patients with mild to moderate renal impairment. Monitoring renal function in patients with renal impairment is recommended.

Hepatic Impairment

• The use of fenofibric acid delayed-release capsules has not been evaluated in subjects with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Choline fenofibrate in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Choline fenofibrate in patients who are immunocompromised.

Administration and Monitoring

Administration

• Oral

• Intravenous

Monitoring

There is limited information regarding Monitoring of Choline fenofibrate in the drug label.

IV Compatibility

There is limited information regarding IV Compatibility of Choline fenofibrate in the drug label.

Overdosage

• There is no specific treatment for overdose with fenofibric acid delayed-release capsules. General supportive care of the patient is indicated, including monitoring of vital signs and observation of clinical status, should an overdose occur. If indicated, elimination of unabsorbed drug should be achieved by emesis or gastric lavage; usual precautions should be observed to maintain the airway. Because fenofibric acid delayed-release capsules are highly bound to plasma proteins, hemodialysis should not be considered.

Pharmacology

There is limited information regarding Choline fenofibrate Pharmacology in the drug label.

Mechanism of Action

• The active moiety of fenofibric acid delayed-release capsules is fenofibric acid. The pharmacological effects of fenofibric acid in both animals and humans have been extensively studied through oral administration of fenofibrate.

• The lipid-modifying effects of fenofibric acid seen in clinical practice have been explained in vivo in transgenic mice and in vitro in human hepatocyte cultures by the activation of peroxisome proliferator activated receptor α (PPARα). Through this mechanism, fenofibric acid increases lipolysis and elimination of triglyceride-rich particles from plasma by activating lipoprotein lipase and reducing production of Apo CIII (an inhibitor of lipoprotein lipase activity).

• The resulting decrease in TG produces an alteration in the size and composition of LDL from small, dense particles (which are thought to be atherogenic due to their susceptibility to oxidation), to large buoyant particles. These larger particles have a greater affinity for cholesterol receptors and are catabolized rapidly. Activation of PPARα also induces an increase in the synthesis of HDL-C and Apo AI and AII.

Structure

There is limited information regarding Choline fenofibrate Structure in the drug label.

Pharmacodynamics

• Elevated levels of Total-C, LDL-C, and Apo B, and decreased levels of HDL-C and its transport complex, Apo AI and Apo AII, are risk factors for human atherosclerosis. Epidemiologic studies have established that cardiovascular morbidity and mortality vary directly with the levels of Total-C, LDL-C, and TG, and inversely with the level of HDL-C. The independent effect of raising HDL-C or lowering TG on the risk of cardiovascular morbidity and mortality has not been determined.

• Fenofibric acid, the active metabolite of fenofibrate, produces reductions in TC, LDL-C, Apo B, TG, and triglyceride-rich lipoprotein (VLDL) in treated patients. In addition, treatment with fenofibric acid results in increases in HDL-C and Apo AI and Apo AII.

Pharmacokinetics

There is limited information regarding Choline fenofibrate Pharmacokinetics in the drug label.

Nonclinical Toxicology

There is limited information regarding Choline fenofibrate Nonclinical Toxicology in the drug label.

Clinical Studies

There is limited information regarding Choline fenofibrate Clinical Studies in the drug label.

How Supplied

There is limited information regarding Choline fenofibrate How Supplied in the drug label.

Storage

There is limited information regarding Choline fenofibrate Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Choline fenofibrate Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Choline fenofibrate interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Choline fenofibrate Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Choline fenofibrate Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.