Lipofen
fenofibrate · Capsule · Oral
Uses
1 INDICATIONS AND USAGE LIPOFEN is indicated as adjunctive therapy to diet: to reduce triglyceride (TG) levels in adults with severe hypertriglyceridemia (TG greater than or equal to 500 mg/dL). to reduce elevated low-density lipoprotein cholesterol (LDL-C) in adults with primary hyperlipidemia when use of recommended LDL-C lowering therapy is not possible. LIPOFEN is a peroxisome proliferator-activated receptor (PPAR) alpha agonist indicated as an adjunct to diet: to reduce triglyceride (TG) levels in adults with severe hypertriglyceridemia (TG greater than or equal to 500 mg/dL) ( 1 ). to reduce elevated low-density lipoprotein cholesterol (LDL-C) in adults with primary hyperlipidemia when use of recommended LDL-C lowering therapy is not possible ( 1 ) Limitations of Use: Markedly elevated levels of serum TG (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 determined ( 1 ). Fenofibrate did not reduce coronary heart disease morbidity and mortality in two large, randomized controlled trials of patients with type 2 diabetes mellitus. ( 1 ) Limitations of Use Markedly elevated levels of serum TG (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 determined [see Warnings and Precautions (5.7) ] . Fenofibrate did not reduce coronary heart disease morbidity and mortality in two large, randomized controlled trials of patients with type 2 diabetes mellitus [see Warnings and Precautions (5.1) and Clinical Studies (14.4) ].
Dosage and administration
Severe hypertriglyceridemia: 50 to 150 mg orally once daily; the dosage should be adjusted according to patient response ( 2.2 ) Primary hyperlipidemia: 150 mg orally once daily ( 2.2 ) Administer as a single dose, at any time of day, with food 2.2 ). Assess TG when clinically appropriate, as early as 4 to 8 weeks after initiating LIPOFEN. Discontinue LIPOFEN in patients who do not have an adequate response after 2 months of treatment ( 2.2 ) Renal impairment : Initial dosage of 50 mg orally once daily ( 2.3 ) Geriatric patients : Select the dosage on the basis of renal function ( 2.4 ) 2.1 Prior to Initiation of LIPOFEN Assess lipid levels before initiating therapy. Identify other causes (e.g., diabetes mellitus, hypothyroidism, or medications) of high TG levels and manage as appropriate. Patients should be placed on an appropriate lipid-lowering diet before receiving LIPOFEN, and should continue this diet during treatment with LIPOFEN. In patients with diabetes and fasting chylomicronemia, improve glycemic control prior to considering starting LIPOFEN. 2.2 Recommended Dosage and Administration Severe hypertriglyceridemia: The recommended dosage of LIPOFEN is 50 mg or 150 mg orally 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. Primary hyperlipidemia: The recommended dosage of LIPOFEN is 150 mg orally once daily. Administer LIPOFEN as a single dose at any time of day, with food. Advise patients to swallow LIPOFEN capsules whole. Do not crush, break, dissolve, or chew capsules. Assess TG when clinically appropriate, as early as 4 to 8 weeks after initiating LIPOFEN. Discontinue LIPOFEN in patients who do not have an adequate response after 2 months of treatment. If a dose is missed, advise patients not to take an extra dose. Resume treatment with the next dose. Advise patients to take LIPOFEN at least 1 hour before or 4 hours to 6 hours after a bile acid binding resin to avoid impeding its absorption. 2.3 Recommended Dosage in Patients with Renal Impairment Assess renal function prior to initiation of LIPOFEN and periodically thereafter [see Warnings and Precautions (5.4) ]. Treatment with LIPOFEN should be initiated at a dosage of 50 mg orally once daily in patients with mild to moderately impaired renal function (eGFR 30 to <60 mL/min/1.73m 2 ), and increased only after evaluation of the effects on renal function and TG levels at this dosage. LIPOFEN is contraindicated in patients with severe renal impairment (eGFR <30 mL/min/1.73m 2 ), including those with end-stage renal disease (ESRD) and those receiving dialysis [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3) ]. 2.4 Recommended Dosage in Geriatric Patients Dosage selection for geriatric patients should be made on the basis of renal function [see Use in Specific Populations (8.5) and Clinical Pharmacology (12.3) ] .
Dosage forms and strengths
50 mg: Size 3 white opaque gelatin capsule imprinted "G 246" and "50" in black ink. 150 mg: Size 1 white opaque gelatin capsule imprinted "G 248" and "150" in green ink. Capsules: 50 mg and 150 mg ( 3 )
Contraindications
4 CONTRAINDICATIONS LIPOFEN is contraindicated in patients with: Severe renal impairment, including those with end-stage renal disease (ESRD) and those receiving dialysis [see Clinical Pharmacology (12.3) ] . Active liver disease, including those with unexplained persistent liver function abnormalities [see Warnings and Precautions (5.2) ] . Pre-existing gallbladder disease [see Warnings and Precautions (5.5) ] . Hypersensitivity to fenofibrate, fenofibric acid, or any of the excipients in LIPOFEN. Serious hypersensitivity reactions including anaphylaxis and angioedema have been reported with fenofibrate [see Warnings and Precautions (5.9) ] . Severe renal impairment, including those with end-stage renal disease (ESRD) and those receiving dialysis ( 4 ) Active liver disease, including those with unexplained persistent liver function abnormalities ( 4 ) Pre-existing gallbladder disease ( 4 ) Hypersensitivity to fenofibrate, fenofibric acid, or any of the excipients in LIPOFEN ( 4 )
Warnings and precautions
Hepatotoxicity : Serious drug-induced liver injury, including liver transplantation and death, has been reported with fenofibrates, including LIPOFEN. Monitor patient's liver function, including serum ALT, AST, and total bilirubin, at baseline and periodically for the duration of therapy. Discontinue if signs or symptoms of liver injury develop or if elevated enzyme levels persist. ( 5.2 ) Myopathy and Rhabdomyolysis : Have been reported in patients taking fenofibrates. Risks are increased during co-administration with a statin, in geriatric patients and in patients with renal impairment, or hypothyroidism. Discontinue LIPOFEN if markedly elevated CK levels occur or if myopathy is either diagnosed or suspected. Temporarily discontinue LIPOFEN in patients experiencing an acute or serious condition at high risk of developing renal failure secondary to rhabdomyolysis. Inform patients of the risk of myopathy and rhabdomyolysis when starting or increasing the LIPOFEN dosage. Instruct patients to promptly report any unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. ( 5.3 ) Increases in Serum Creatinine : Monitor renal function in patients with renal impairment taking LIPOFEN. Consider monitoring renal function in patients at risk for renal impairment. ( 5.4 ) Cholelithiasis : Fenofibrate may increase cholesterol excretion into the bile, leading to cholelithiasis. If cholelithiasis is suspected, gallbladder studies are indicated. ( 5.5 ) Hypersensitivity Reactions : Acute hypersensitivity reactions, including anaphylaxis and angioedema and delayed hypersensitivity reactions, including severe cutaneous adverse drug reactions have been reported postmarketing. Some cases were life-threatening and required emergency treatment. Discontinue LIPOFEN and treat appropriately if reactions occur. ( 5.9 ) 5.1 Mortality and Coronary Heart Disease Morbidity Fenofibrate did not reduce cardiovascular disease morbidity or mortality in two large, randomized controlled trials of patients with type 2 diabetes mellitus [see Clinical Studies (14.4) ]. Because of chemical, pharmacological, and clinical similarities between fenofibrates, including LIPOFEN; pemafibrate; clofibrate; and gemfibrozil; the findings in 5 large randomized, placebo-controlled clinical trials with these other fibrate drugs may also apply to LIPOFEN. Pemafibrate did not reduce cardiovascular disease morbidity or mortality in a large, randomized, placebo-controlled trial of patients with type 2 diabetes mellitus on background statin therapy [see Clinical Studies (14.4) ]. In the Coronary Drug Project, a large trial conducted from 1965 to 1985 in men post myocardial infarction, there was no difference in mortality or nonfatal myocardial infarction between the clofibrate group and the placebo group after 5 years of treatment (NCT00000482). In a trial conducted by the World Health Organization (WHO) from 1965 to 1976, men without known coronary artery disease were treated with placebo or clofibrate for 5 years and followed for an additional 1 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. The Helsinki Heart Study, conducted from 1982 to 1987, was a large (n=4,081) trial 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 but not statistically higher in the gemfibrozil randomization group versus placebo [95% confidence interval (CI) of the hazard ratio (HR) 0.91 to 1.64]. A secondary prevention component of the Helsinki Heart Study treated middle-aged men with gemfibrozil or placebo for 5 years. The HR for cardiac deaths was 2.2, 95% CI, 0.94 to 5.05. 5.2 Hepatotoxicity Serious drug-induced liver injury (DILI), including liver transplantation and death, has been reported with postmarketing use of fenofibrates, including LIPOFEN. 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 LIPOFEN 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, an intermediate daily dosage or the maximum recommended daily dosage of fenofibrate have been associated with increases in serum AST or ALT. The incidence of increases in transaminases may be dose related [see Adverse Reactions (6.1) ] . LIPOFEN is contraindicated in patients with active liver disease, including those with 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 LIPOFEN. Discontinue LIPOFEN 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 LIPOFEN in these patients if there is no alternative explanation for the liver injury. 5.3 Myopathy and Rhabdomyolysis LIPOFEN may cause myopathy [muscle pain, tenderness, or weakness associated with elevated creatine kinase (CK)] and rhabdomyolysis.
Side effects
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) ] Myopathy and Rhabdomyolysis [see Warnings and Precautions (5.3) ] Increases in Serum Creatinine [see Warnings and Precautions (5.4) ] Cholelithiasis [see Warnings and Precautions (5.5) ] Increased Bleeding Risk with Coumarin Anticoagulants [see Warnings and Precautions (5.6) ] Pancreatitis [see Warnings and Precautions (5.7) ] Hematologic Changes [see Warnings and Precautions (5.8) ] Hypersensitivity reactions [see Warnings and Precautions (5.9) ] Venothromboembolic disease [see Warnings and Precautions (5.10) ] Paradoxical Decreases in HDL Cholesterol Levels [see Warnings and Precautions (5.11) ] Adverse reactions (≥ 2% and greater than placebo): abnormal liver tests, increased AST, increased ALT, increased CPK, and rhinitis ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact ANI Pharmaceuticals, Inc. at 1-855-204-1431 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The safety of LIPOFEN has been established in adults with hypertriglyceridemia or primary hyperlipidemia based on adequate and well-controlled trials of other formulations of fenofibrate, referenced below as "fenofibrate" [see Clinical Studies (14) ]. Dosages of fenofibrate used in these trials were comparable to LIPOFEN 150 mg per day [see Clinical Pharmacology (12.3) ]. Adverse reactions reported by 2% or more of patients treated with fenofibrate (and greater than placebo) during the double-blind, placebo-controlled trials are listed in Table 1 below. Adverse reactions led to discontinuation of treatment in 5% of patients treated with fenofibrate and in 3% 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 Adverse Reaction Placebo (N =365) Fenofibrate (N = 439) Abnormal Liver Tests 1% 8% Abdominal Pain 4% 5% Increased ALT 2% 3% Increased AST 1% 3% Increased Creatine Phosphokinase 1% 3% Constipation 1% 2% Rhinitis 1% 2% Other Adverse Reactions Urticaria 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 either an intermediate or the maximum recommended daily dosage of fenofibrate versus 1.1% of patients treated with placebo . In an 8-week trial, the incidence of ALT or AST elevations ≥ 3 times the upper limit of normal was 13% in patients receiving an intermediate daily dosage or the maximum recommended daily dosage of fenofibrate and was 0% in those receiving the lowest recommended daily dosage of fenofibrate or placebo [see Warnings and Precautions (5.2) ] . 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval 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: Blood: Anemia, white blood cell decreases Gastrointestinal: Pancreatitis General: Asthenia Hepatobiliary: Increased total bilirubin, hepatitis, cirrhosis Immune System: Anaphylaxis, angioedema Lipid Disorders: Severely depressed HDL-cholesterol levels Musculoskeletal: Myalgia, muscle spasms, rhabdomyolysis, arthralgia Renal and Urinary: Acute renal failure Respiratory: Interstitial lung disease Skin and Subcutaneous Tissue: Photosensitivity reactions, days to months after initiation. This may occur in patients who report a prior photosensitivity reaction to ketoprofen.
Drug interactions
Table 2 presents clinically important drug interactions with LIPOFEN. Table 2: Clinically Important Drug Interactions with LIPOFEN Statins Clinical Impact: Fibrates may cause myopathy when given alone. The risk of myopathy and rhabdomyolysis is increased with concomitant use of fibrates with statins. Intervention: Consider if the benefit of using LIPOFEN concomitantly with statin therapy outweighs the increased risk of myopathy and rhabdomyolysis. If concomitant use is decided, monitor patients for signs and symptoms of myopathy, particularly during initiation of therapy and during upward dosage titration of statin therapy. Colchicine Clinical Impact: Cases of myopathy and rhabdomyolysis have been reported with concomitant use of colchicine with fenofibrates. Intervention: Consider if the benefit of using colchicine concomitantly with LIPOFEN outweighs the increased risk of myopathy and rhabdomyolysis. If concomitant use is decided, monitor patients for signs and symptoms of myopathy, particularly during initiation of therapy and during upward dosage titration of colchicine. Coumarin Anticoagulants Clinical Impact: Fibrates may cause potentiation of coumarin-type anticoagulant effects with prolongation of the PT/INR. Intervention: Caution should be exercised when coumarin anticoagulants are given in conjunction with LIPOFEN. 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 Clinical Impact: 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 LIPOFEN, there is a risk that an interaction will lead to deterioration of renal function. Intervention: The benefits and risks of using LIPOFEN with immunosuppressants and other potentially nephrotoxic agents should be carefully considered, and the lowest effective dosage employed and renal function monitored. Bile-Acid Binding Resins Clinical Impact: Bile-acid binding resins may bind other drugs given concurrently. Intervention: In patients taking a bile acid resin, administer LIPOFEN at least 1 hour before or 4 to 6 hours after the bile acid resin to avoid impeding its absorption. Consider if the benefit of concomitant use of statins or colchicine outweighs the increased risk of myopathy and rhabdomyolysis. Monitor patients for signs and symptoms of myopathy ( 7 ) Exercise caution in concomitant treatment with coumarin anticoagulants. Reduce the dosage of coumarin to maintain the PT/INR at the desired level to prevent bleeding complications ( 7 ). Consider the benefits and risks of concomitant use with immunosuppressants and other potentially nephrotoxic agents. Use the lowest effective dosage and monitor renal function ( 7 ). Administer LIPOFEN at least 1 hour before or 4 to 6 hours after a bile acid resin to avoid impeding its absorption ( 7 ).
Use in specific populations
8.1 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 comparable to the maximum recommended clinical dosage of 150 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 ). LIPOFEN 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 mg/kg/day, 127 mg/kg/day, 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 [MRHD] of 300 mg fenofibrate daily, comparable to 150 mg LIPOFEN 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 mg/kg/day, 150 mg/kg/day, 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 mg/kg/day, 75 mg/kg/day, 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. 8.2 Lactation Risk Summary There is no available information on the presence of fenofibrate in human milk, effects of the drug on the breastfed infant, or the effects on milk production. Fenofibrate is present in the milk of rats, and is therefore likely to be present in human milk. Because of the potential for serious adverse reactions in breastfed infants, such as disruption of infant lipid metabolism, women should not breastfeed during treatment with LIPOFEN and for 5 days after the final dose 8.4 Pediatric Use The safety and effectiveness of LIPOFEN have not been established in pediatric patients with severe hypertriglyceridemia or primary hyperlipidemia. 8.5 Geriatric Use Assess renal function in geriatric patients and follow contraindications and dosing recommendations for patients with renal impairment [see Contraindications (4) , Warnings and Precautions (5.3 , 5.4) , and Use in Specific Populations (8.6) . While fenofibric acid exposure is not influenced by age, geriatric patients are more likely to have renal impairment, and fenofibric acid is substantially excreted by the kidney [see Clinical Pharmacology (12.3) ]. Consider monitoring renal function in geriatric patients taking LIPOFEN. 8.6 Renal Impairment LIPOFEN is contraindicated in patients with severe renal impairment (eGFR <30 mL/min/1.73m 2 ) including those with end-stage renal disease (ESRD) and those receiving dialysis. Dosage reduction is required in patients with mild to moderate renal impairment [see Dosage and Administration (2.4) and Clinical Pharmacology (12.3) ] . Patients with severe renal impairment have 2.7-fold higher exposure of fenofibric acid and increased accumulation of fenofibric acid during chronic dosing compared with healthy volunteers. Renal impairment is a risk factor for myopathy and rhabdomyolysis [ see Warnings and Precautions (5.3 , 5.4) , and Clinical Pharmacology (12.3) ]. 8.7 Hepatic Impairment The use of LIPOFEN has not been evaluated in patients with hepatic impairment. LIPOFEN is contraindicated in patients with active liver disease, including those with unexplained persistent liver function abnormalities [ Clinical Pharmacology (12.3) ].
Pregnancy
8.1 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 comparable to the maximum recommended clinical dosage of 150 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 ). LIPOFEN 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 mg/kg/day, 127 mg/kg/day, 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 [MRHD] of 300 mg fenofibrate daily, comparable to 150 mg LIPOFEN 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 mg/kg/day, 150 mg/kg/day, 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 mg/kg/day, 75 mg/kg/day, 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
8.4 Pediatric Use The safety and effectiveness of LIPOFEN have not been established in pediatric patients with severe hypertriglyceridemia or primary hyperlipidemia.
Geriatric use
8.5 Geriatric Use Assess renal function in geriatric patients and follow contraindications and dosing recommendations for patients with renal impairment [see Contraindications (4) , Warnings and Precautions (5.3 , 5.4) , and Use in Specific Populations (8.6) . While fenofibric acid exposure is not influenced by age, geriatric patients are more likely to have renal impairment, and fenofibric acid is substantially excreted by the kidney [see Clinical Pharmacology (12.3) ]. Consider monitoring renal function in geriatric patients taking LIPOFEN.
Overdosage
In the event of an overdose of LIPOFEN, consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdosage management recommendations. There is no specific treatment for overdose with LIPOFEN. 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.
Description
11 DESCRIPTION LIPOFEN ® (fenofibrate capsules, USP), is a peroxisome proliferator-activated receptor (PPAR) alpha agonist available as hard gelatin capsules for oral administration. Each hard gelatin capsule contains 50 or 150 mg of fenofibrate USP. The chemical name for fenofibrate is 2-[4-(4-chlorobenzoyl) phenoxy]-2-methyl-propanoic acid, 1-methylethyl ester with the following structural formula: The empirical formula is C 20 H 21 O 4 Cl and the molecular weight is 360.83; fenofibrate is insoluble in water. The melting point is 79-82°C. Fenofibrate is a white solid which is stable under ordinary conditions. LIPOFEN (fenofibrate capsules, USP) meets USP Dissolution Test 2. Inactive Ingredients: Each hard gelatin capsule contains Gelucire 44/14 (lauroyl macrogol glyceride type 1500), polyethylene glycol 20,000, polyethylene glycol 8000, hydroxypropylcellulose, sodium starch glycolate, gelatin, titanium dioxide, shellac, propylene glycol, may also contain black iron oxide, FD&C Blue #1, FD&C Blue #2, FD&C Red #40, D&C Yellow #10. Chemical Structure
Mechanism of action
12.1 Mechanism of Action The active moiety of LIPOFEN is fenofibric acid. The pharmacological effects of fenofibric acid in both animals and humans have been 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 PPAR alpha receptor. Through this mechanism, fenofibric acid increases lipolysis and elimination of triglyceride-rich particles from plasma by activating lipoprotein lipase and reducing production of apoprotein C-III (an inhibitor of lipoprotein lipase activity).
How supplied
16 HOW SUPPLIED/STORAGE AND HANDLING LIPOFEN ® (fenofibrate) capsules is available in two strengths: Strength Description NDC Package Size (capsules per bottle) 50 mg Size 3 white opaque/white opaque gelatin capsule, imprinted in black ink with "50" between lines on the body, "G 246" on the cap and containing a white to almost white paste NDC 62559-305-90 90 150 mg Size 1 white opaque/white opaque gelatin capsule, imprinted in green ink with "150" between lines on the body, "G 248" on the cap and containing a white to almost white paste NDC 62559-306-90 90 Storage Store at 25ºC; Excursions permitted to 15ºC - 30ºC (59ºF - 86ºF). [See USP Controlled Room Temperature]. Keep out of the reach of children. Protect from moisture and light.
Storage
Storage Store at 25ºC; Excursions permitted to 15ºC - 30ºC (59ºF - 86ºF). [See USP Controlled Room Temperature]. Keep out of the reach of children. Protect from moisture and light.
Patient information
Hepatotoxicity Inform patients that LIPOFEN may cause liver enzyme elevations and possibly liver failure. Advise patients to promptly report fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice [see Contraindications (4) and Warnings and Precautions (5.2) ] . Myopathy and Rhabdomyolysis Advise patients that LIPOFEN may cause myopathy and rhabdomyolysis. Inform patients that the risk is also increased when taking certain types of medication and they should discuss all medication, both prescription and over the counter, with their healthcare provider. Instruct patients to inform other healthcare providers prescribing a new medication or increasing the dosage of an existing medication that they are taking LIPOFEN. Instruct patients to promptly report any unexplained muscle pain, tenderness, or weakness particularly if accompanied by malaise or fever [see Warnings and Precautions (5.3) and Drug Interactions (7) ] . Increased Bleeding Risk with Coumarin Anticoagulants Inform patients that the concomitant use of LIPOFEN with coumarin-type anticoagulants may increase the risk of bleeding. Advise patients if they are taking or planning to take coumarin-type anticoagulants to inform their healthcare providers and that increased monitoring may be necessary [see Warnings and Precautions (5.6) and Drug Interactions (7) ]. Hypersensitivity Reactions Inform patients that serious hypersensitivity reactions, such as anaphylaxis and angioedema, have been reported with fenofibrates. Advise patients to report immediately any signs or symptoms suggesting allergic reaction, and to discontinue drug until they have consulted prescribing physicians [see Warnings and Precautions (5.9) ] . Pregnancy Advise patients to inform their healthcare provider of a known or suspected pregnancy to discuss if LIPOFEN should be discontinued [see Use in Specific Populations (8.1) ] . Lactation Advise patients that breastfeeding during treatment with LIPOFEN is not recommended [see Use in Specific Populations (8.2) ]. Missed Doses If a dose is missed, advise patients not take an extra dose and to resume treatment with the next dose.
Label text from the FDA structured product label by ANI Pharmaceuticals, Inc. (revised May 12, 2026). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Fenofibrate in 2 products
Lipofen NDC products (2)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 62559-305 | Fenofibrate 50 mg/1 Capsule | ANI Pharmaceuticals, Inc. | NDA |
| 62559-306 | Fenofibrate 150 mg/1 Capsule | ANI Pharmaceuticals, Inc. | NDA |
Frequently asked questions
What is Lipofen used for?
1 INDICATIONS AND USAGE LIPOFEN is indicated as adjunctive therapy to diet: to reduce triglyceride (TG) levels in adults with severe hypertriglyceridemia (TG greater than or equal to 500 mg/dL). to reduce elevated low-density lipoprotein cholesterol (LDL-C) in adults with primary hyperlipidemia when use of recommended LDL-C lowering therapy is not possible. LIPOFEN is a peroxisome…
What are the side effects of Lipofen?
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) ] Myopathy and Rhabdomyolysis [see Warnings and Precautions (5.3) ] Increases in Serum Creatinine [see Warnings and Precautions (5.4) ] Cholelithiasis [see Warnings and… See the full label for the complete list.
Who makes Lipofen?
Lipofen is listed by 1 labeler in the FDA NDC directory, including ANI Pharmaceuticals, Inc..