Fenofibrate Drug Information
Generic name: FENOFIBRATE
Peroxisome Proliferator Receptor alpha Agonist [EPC]
Uses of Fenofibrate
Primary Hypercholesterolemia or Mixed Dyslipidemia Fenofibrate tablet
USP is indicated as adjunctive therapy to diet to reduce elevated low-density lipoprotein cholesterol (LDL-C), total cholesterol (Total-C), Triglycerides and apolipoprotein B (Apo B), and to increase high-density lipoprotein cholesterol (HDL-C) in adult patients with primary hypercholesterolemia or mixed dyslipidemia.
Severe Hypertriglyceridemia Fenofibrate tablet
USP is also indicated as adjunctive therapy to diet for treatment of adult patients with severe hypertriglyceridemia. Improving glycemic control in diabetic patients showing fasting chylomicronemia will usually obviate the need for pharmacologic intervention. Markedly elevated levels of serum triglycerides (e.g. > 2,000 mg/dL) may increase the risk of developing pancreatitis.
The effect of fenofibrate therapy on reducing this risk has not been adequately studied.
Important Limitations of Use Fenofibrate at a dose equivalent to 160 mg
of fenofibrate tablet USP was not shown to reduce coronary heart disease morbidity and mortality in a large, randomized controlled trial of patients with type 2 diabetes mellitus .
Dosage & Administration of Fenofibrate
General Considerations Patients should be placed on an appropriate lipid-lowering diet before
receiving fenofibrate tablet USP, and should continue this diet during treatment with fenofibrate tablet USP. Fenofibrate tablets USP should be given with meals, thereby optimizing the bioavailability of the medication. The initial treatment for dyslipidemia is dietary therapy specific for the type of lipoprotein abnormality. Excess body weight and excess alcoholic intake may be important factors in hypertriglyceridemia and should be addressed prior to any drug therapy.
Physical exercise can be an important ancillary measure. Diseases contributory to hyperlipidemia, such as hypothyroidism or diabetes mellitus should be looked for and adequately treated. Estrogen therapy, thiazide diuretics and beta-blockers, are sometimes associated with massive rises in plasma triglycerides, especially in subjects with familial hypertriglyceridemia.
In such cases, discontinuation of the specific etiologic agent may obviate the need for specific drug therapy of hypertriglyceridemia. Lipid levels should be monitored periodically and consideration should be given to reducing the dosage of fenofibrate tablet USP if lipid levels fall significantly below the targeted range. Therapy should be withdrawn in patients who do not have an adequate response after two months of treatment with the maximum recommended dose of 160 mg once daily.
Primary Hypercholesterolemia or Mixed Dyslipidemia
The initial dose of fenofibrate tablet USP is 160 mg once daily.
Severe Hypertriglyceridemia
The initial dose is 54 to 160 mg per day. 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 160 mg once daily.
Impaired Renal Function Treatment with fenofibrate tablet
USP should be initiated at a dose of 54 mg per day in patients having mild to moderately impaired renal function, and increased only after evaluation of the effects on renal function and lipid levels at this dose. The use of fenofibrate tablet USP should be avoided in patients with severe renal impairment.
Geriatric Patients Dose selection for the elderly should be made on the
basis of renal function .
Side Effects of Fenofibrate
- The following serious adverse reactions are described below and elsewhere in the labeling:
- Mortality and coronary heart disease morbidity [see WARNINGS AND PRECAUTIONS ( 5.1 )]
- Hepatoxicity [see WARNINGS AND PRECAUTIONS ( 5.2 )]
- Pancreatitis [see WARNINGS AND PRECAUTIONS ( 5.7 )]
- Hypersensitivity reactions [see WARNINGS AND PRECAUTIONS ( 5.9 )]
- Venothromboembolic disease [see WARNINGS AND PRECAUTIONS ( 5.10 )] Adverse reactions > 2% and at least 1% greater than placebo: Abnormal liver tests, increased AST, increased ALT, increased CPK, and rhinitis ( 6 ). To report SUSPECTED ADVERSE REACTIONS, contact Lupin Pharmaceuticals, Inc. at 1-800-399-2561 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. Adverse events reported by 2% or more of patients treated with fenofibrate (and greater than placebo) during the double-blind, placebo-controlled trials, regardless of causality, are listed in Table 1 below. 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 function tests were the most frequent events, causing discontinuation of fenofibrate treatment in 1.6% of patients in double- blind trials. Table 1. Adverse Reactions Reported by 2% or More of Patients Treated with Fenofibrate and Greater than Placebo During the Double-Blind, Placebo-Controlled Trials 1 Significantly different from Placebo. BODY SYSTEM Fenofibrate Dosage equivalent to 160 mg fenofibrate. Placebo Adverse Reaction ( N = 439 ) ( N = 365 ) BODY AS A WHOLE Abdominal Pain 4.6% 4.4% Back Pain 3.4% 2.5% Headache 3.2% 2.7% DIGESTIVE Nausea 2.3% 1.9% Constipation 2.1% 1.4% METABOLIC AND NUTRITIONAL DISORDERS Abnormal Liver Function Tests 7.5% 1 1.4% Increased ALT 3.0% 1.6% Increased CPK 3.0% 1.4% Increased AST 3.4% 1 0.5% RESPIRATORY Respiratory Disorder 6.2% 5.5% Rhinitis 2.3% 1.1% Urticaria was seen in 1.1% vs. 0%, and rash in 1.4% vs. 0.8% of fenofibrate and placebo patients respectively in controlled trials. Increases in Liver Enzymes In a pooled analysis of 10 placebo-controlled trials, increases to > 3 times the upper limit of normal in ALT occurred in 5.3% of patients taking fenofibrate at doses equivalent to 107 mg to 160 mg fenofibrate daily versus 1.1% of patients treated with placebo. In an 8-week study, the incidence of ALT or AST elevations ≥ 3 times the upper limit of normal was 13% in patients receiving dosages equivalent to 107 mg to 160 mg fenofibrate daily and was 0% in those receiving dosages equivalent to 54 mg or less fenofibrate daily or placebo. 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of fenofibrate. Because these reactions 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: myalgia, rhabdomyolysis, pancreatitis, acute renal failure, muscle spasm, hepatitis, cirrhosis, increased total bilirubin, anemia, arthralgia, decreases in hemoglobin, decreases in hematocrit, white blood cell decreases, asthenia, severely depressed HDL-cholesterol levels, and interstitial lung disease. Photosensitivity reactions have occurred days to months after initiation; in some of these cases, patients reported a prior photosensitivity reaction to ketoprofen.
Warnings & Cautions for Fenofibrate
Mortality and Coronary Heart Disease Morbidity
The effect of fenofibrate on coronary heart disease morbidity and mortality and non-cardiovascular mortality has not been established. 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 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 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, p=0.04). There was a non-significant 11% (HR 1.11, p=0.18) and 19% (HR 1.19, p=0.22) increase in total and coronary heart disease mortality, respectively, with fenofibrate as compared to placebo. Because of chemical, pharmacological, and clinical similarities between fenofibrate tablets, clofibrate, and gemfibrozil, the adverse findings in 4 large randomized, placebo- controlled clinical studies with these other fibrate drugs may also apply to fenofibrate. In the Coronary Drug Project, a large study of post myocardial infarction of 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 =.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 World Health Organization 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). The rate of gallbladder surgery was not statistically significant between study groups, but did trend higher in the gemfibrozil group, (1.9% vs. 0.3%, p = 0.07).
Hepatotoxicity Serious drug-induced liver injury (DILI), including liver transplantation and death, have
been reported postmarketing with fenofibrate. DILI has been reported within the first few weeks of treatment or after several months of therapy and in some cases has reversed with discontinuation of fenofibrate treatment. Patients with DILI have experienced signs and symptoms including dark urine, abnormal stool, jaundice, malaise, abdominal pain, myalgia, weight loss, pruritus, and nausea.
Many patients had concurrent elevations of total bilirubin, serum alanine transaminase (ALT), and aspartate transaminase (AST). DILI has been characterized as hepatocellular, chronic active, and cholestatic hepatitis, and cirrhosis has occurred in association with chronic active hepatitis. In clinical trials, fenofibrate at doses equivalent to 107 mg to 160 mg fenofibrate daily has been associated with increases in serum AST or ALT. The incidence of increases in transaminases may be dose related. Fenofibrate is contraindicated in patients with active liver disease, including those with primary biliary cirrhosis and unexplained persistent liver function abnormalities.
Monitor patient's liver function, including serum ALT, AST, and total bilirubin, at baseline and periodically for the duration of therapy with fenofibrate. Discontinue fenofibrate if signs or symptoms of liver injury develop or if elevated enzyme levels persist (ALT or AST > 3 times the upper limit of normal, or if accompanied by elevation of bilirubin). Do not restart fenofibrate in these patients if there is no alternative explanation for the liver injury.
Myopathy and Rhabdomyolysis Fibrates increase the risk for myopathy and have been
associated with rhabdomyolysis. The risk for serious muscle toxicity appears to be increased in elderly patients and in patients with diabetes, renal insufficiency, or hypothyroidism. Myopathy should be considered in any patient with diffuse myalgias, muscle tenderness or weakness, and/or marked elevations of creatine phosphokinase (CPK) levels.
Patients should be advised to report promptly unexplained muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever. CPK levels should be assessed in patients reporting these symptoms, and fenofibrate therapy should be discontinued if markedly elevated CPK levels occur or myopathy/myositis is suspected or diagnosed. Data from observational studies indicate that the risk for rhabdomyolysis is increased when fibrates, in particular gemfibrozil, are co-administered with a statin.
The combination should be avoided unless the benefit of further alterations in lipid levels is likely to outweigh the increased risk of this drug combination. Cases of myopathy, including rhabdomyolysis, have been reported with fenofibrates coadministered with colchicine, and caution should be exercised when prescribing fenofibrate with colchicine .
Serum Creatinine Elevations in serum creatinine have been reported in patients on
fenofibrate. These elevations tend to return to baseline following discontinuation of fenofibrate. The clinical significance of these observations is unknown.
Monitor renal function in patients with renal impairment taking fenofibrate. Renal monitoring should also be considered for patients taking fenofibrate at risk for renal insufficiency such as the elderly and patients with diabetes.
Cholelithiasis Fenofibrate, like clofibrate and gemfibrozil, may increase cholesterol excretion into the
bile, leading to cholelithiasis. If cholelithiasis is suspected, gallbladder studies are indicated. Fenofibrate therapy should be discontinued if gallstones are found.
Coumarin Anticoagulants Caution should be exercised when coumarin anticoagulants are given in
conjunction with fenofibrate because of the potentiation of coumarin-type anticoagulant effects in prolonging the Prothrombin Time/International Normalized Ratio (PT/INR). To prevent bleeding complications, frequent monitoring of PT/INR and dose adjustment of the anticoagulant are recommended until PT/INR has stabilized .
Pancreatitis Pancreatitis has been reported in patients taking fenofibrate, gemfibrozil, and clofibrate.
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.
Hematologic Changes Mild to moderate hemoglobin, hematocrit, and white blood cell decreases
have been observed in patients following initiation of fenofibrate therapy. However, these levels stabilize during long- term administration. Thrombocytopenia and agranulocytosis have been reported in individuals treated with fenofibrate.
Periodic monitoring of red and white blood cell counts are recommended during the first 12 months of fenofibrate administration.
Hypersensitivity Reactions Acute Hypersensitivity Anaphylaxis and angioedema have been reported postmarketing with
fenofibrate. In some cases, reactions were life-threatening and required emergency treatment. If a patient develops signs or symptoms of an acute hypersensitivity reaction, advise them to seek immediate medical attention and discontinue fenofibrate.
Delayed Hypersensitivity Severe cutaneous adverse drug reactions (SCAR), including Stevens-Johnson syndrome, toxic epidermal necrolysis, and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), have been reported postmarketing, occurring days to weeks after initiation of fenofibrate. The cases of DRESS were associated with cutaneous reactions (such as rash or exfoliative dermatitis) and a combination of eosinophilia, fever, systemic organ involvement (renal, hepatic, or respiratory). Discontinue fenofibrate and treat patients appropriately if SCAR is suspected. 5.10 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 pulmonary embolism or thrombophlebitis than the placebo group (5.2% vs. 3.3% at five years; p < 0.01). 5.11 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.
Drug Interactions with Fenofibrate
Coumarin Anticoagulants Potentiation of coumarin-type anticoagulant effects has been observed with prolongation
of the PT/INR. Caution should be exercised when coumarin anticoagulants are given in conjunction with fenofibrate. The dosage of the anticoagulants 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 .
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 fibrate drugs including fenofibrate, there is a risk that an interaction will lead to deterioration of renal function. The benefits and risks of using fenofibrate tablet with immunosuppressants and other potentially nephrotoxic agents should be carefully considered, and the lowest effective dose employed and renal function monitored.
Bile Acid Binding Resins
Since bile acid binding resins may bind other drugs given concurrently, patients should take fenofibrate at least 1 hour before or 4 to 6 hours after a bile acid binding resin to avoid impeding its absorption.
Colchicine Cases of myopathy, including rhabdomyolysis, have been reported with fenofibrates co
administered with colchicine, and caution should be exercised when prescribing fenofibrate with colchicine.
Pregnancy Safety for Fenofibrate
Pregnancy Risk Summary Limited available data with fenofibrate use in pregnant women are insufficient to determine a drug associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. In animal reproduction studies, no evidence of embryo-fetal toxicity was observed with oral administration of fenofibrate in rats and rabbits during organogenesis at doses less than or equivalent to the maximum recommended clinical dose of 160 mg daily, based on body surface area (mg/m 2 ). Adverse reproductive outcomes occurred at higher doses in the presence of maternal toxicity (see Data). Fenofibrate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data 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, no adverse developmental findings were observed at 14 mg/kg/day (less than the clinical exposure at the maximum recommended human dose of 300 mg fenofibrate daily, equivalent to 160 mg fenofibrate tablets daily, based on body surface area comparisons). Increased fetal skeletal malformations were observed at maternally toxic doses (361 mg/kg/day, corresponding to 12 times the clinical exposure at the MRHD) that significantly suppressed maternal body weight gain. 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, no adverse developmental findings were observed at 15 mg/kg/day (a dose that approximates the clinical exposure at the MRHD, based on body surface area comparisons). Aborted litters were observed at maternally toxic doses (≥ 150 mg/kg/day, corresponding to ≥ 10 times the clinical exposure at the MRHD) that suppressed maternal body weight gain.
In pregnant rats given oral dietary doses of 15, 75, and 300 mg/kg/day from gestation day 15 through lactation day 21 (weaning), no adverse developmental effects were observed at 15 mg/kg/day (less than the clinical exposure at the MRHD, based on body surface area comparisons), despite maternal toxicity (decreased weight gain). Post-implantation loss was observed at ≥ 75 mg/kg/day (≥ 2 times the clinical exposure at the MRHD) in the presence of maternal toxicity (decreased weight gain). Decreased pup survival was noted at 300 mg/kg/day (10 times the clinical exposure at the MRHD), which was associated with decreased maternal body weight gain/maternal neglect.
Pediatric Use of Fenofibrate
Pediatric Use Safety and effectiveness have not been established in pediatric patients.
Contraindications for Fenofibrate
Severe renal dysfunction, including dialysis patients. Active liver disease. Gallbladder disease.
Known hypersensitivity to fenofibrate. Nursing mothers. Fenofibrate is 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 known hypersensitivity to fenofibrate or fenofibric acid.
Overdosage Information for Fenofibrate
There is no specific treatment for overdose with fenofibrate. 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 is highly bound to plasma proteins, hemodialysis should not be considered.
Clinical Studies of Fenofibrate
Primary Hypercholesterolemia (Heterozygous Familial and Nonfamilial) and Mixed Dyslipidemia
The effects of fenofibrate at a dose equivalent to 160 mg fenofibrate per day were assessed from four randomized, placebo-controlled, double-blind, parallel-group studies including patients with the following mean baseline lipid values: total-C 306.9 mg/dL; LDL-C 213.8 mg/dL; HDL-C 52.3 mg/dL; and triglycerides 191.0 mg/dL. Fenofibrate therapy lowered LDL-C, Total-C, and the LDL-C/HDL-C ratio. Fenofibrate therapy also lowered triglycerides and raised HDL-C (see Table 4). Table 4. Mean Percent Change in Lipid Parameters at End of Treatment Duration of study treatment was 3 to 6 months. 1 p = < 0.05 vs. Placebo Treatment Group Total - C LDL - C HDL - C TG Pooled Cohort Mean baseline lipid values (n=646) 306.9 mg/dL 213.8 mg/dL 52.3 mg/dL 191.0 mg/dL All FEN (n=361) -18.7% 1 -20.6% 1 +11.0% 1 -28.9% 1 Placebo (n=285) -0.4% -2.2% +0.7% +7.7% Baseline LDL - C > 160 mg / dL and TG < 150 mg / dL Mean baseline lipid values (n=334) 307.7 mg/dL 227.7 mg/dL 58.1 mg/dL 101.7 mg/dL All FEN (n=193) -22.4% 1 -31.4% 1 +9.8% 1 -23.5% 1 Placebo (n=141) +0.2% -2.2% +2.6% +11.7% Baseline LDL - C > 160 mg / dL and TG ≥ 150 mg / dL Mean baseline lipid values (n=242) 312.8 mg/dL 219.8 mg/dL 46.7 mg/dL 231.9 mg/dL All FEN (n=126) -16.8% 1 -20.1% 1 +14.6% 1 -35.9% 1 Placebo (n=116) -3.0% -6.6% +2.3% +0.9% In a subset of the subjects, measurements of apo B were conducted.
Fenofibrate treatment significantly reduced apo B from baseline to endpoint as compared with placebo (-25.1% vs. 2.4%, p < 0.0001, n=213 and 143 respectively).
Severe Hypertriglyceridemia
The effects of fenofibrate on serum triglycerides were studied in two randomized, double-blind, placebo-controlled clinical trials of 147 hypertriglyceridemic patients. Patients were treated for eight weeks under protocols that differed only in that one entered patients with baseline TG levels of 500 to 1500 mg/dL, and the other TG levels of 350 to 500 mg/dL. In patients with hypertriglyceridemia and normal cholesterolemia with or without hyperchylomicronemia, treatment with fenofibrate at dosages equivalent to fenofibrate 160 mg per day decreased primarily very low density lipoprotein (VLDL) triglycerides and VLDL cholesterol. Treatment of patients with elevated triglycerides often results in an increase of LDL-C (see Table 5). Table 5. Effects of Fenofibrate in Patients With Severe Hypertriglyceridemia * =p < 0.05 vs.
Placebo S tudy 1 Placebo Fenofibrate Ba s eline TG levels 350 N Ba s eline En d p o int % Change N Ba s eline En d p o int % Change to 499 mg/dL ( M ean) ( M ean) ( M ean) ( M ean) ( M ean) ( M ean) Triglycerides 28 449 450 -0.5 27 432 223 -46.2 * VLDL Triglycerides 19 367 350 2.7 19 350 178 -44.1 * Total Cholesterol 28 255 261 2.8 27 252 227 -9.1 * HDL Cholesterol 28 35 36 4 27 34 40 19.6 * LDL Cholesterol 28 120 129 12 27 128 137
VLDL Cholesterol 27 99 99 5.8 27 92 46 -44.7 * S
tudy 2 P l acebo Fenofibrate Ba s eline TG levels 500 N Ba s eline En d p o int % Change N Ba s eline En d p o int % Change to 1500 mg/dL ( M ean) ( M ean) ( M ean) (M ean) ( M ean) ( M ean) Triglycerides 44 710 750 7.2 48 726 308 -54.5 * VLDL Triglycerides 29 537 571 18.7 33 543 205 -50.6 * Total Cholesterol 44 272 271 0.4 48 261 223 -13.8 * HDL Cholesterol 44 27 28 5.0 48 30 36 22.9 * LDL Cholesterol 42 100 90 -4.2 45 103 131 45.0 * VLDL Cholesterol 42 137 142 11.0 45 126 54 -49.4 * The effect of fenofibrate on cardiovascular morbidity and mortality has not been determined.
Drug information sourced from the FDA. This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before making any medication decisions.
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