Enter drug's generic or brand name below. Results will appear here. Note: all drug related information obtained on this page is provided by RX List.
Using the RX LIST database:
(1) Enter the drug name in the search box below and hit ENTER
(2) The rx list web site will open here with the drug search completed. Next, scroll down the page to locate the link to the drug you are searching for and then click on the link.
Triglide (fenofibrate) Tablets, is a lipid regulating agent available as tablets for oral administration. Each tablet contains 160 mg of fenofibrate. 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 C20H21O4Cl and the molecular weight is 360.83; fenofibrate is insoluble in water. The melting point is 79° to 82°C. Fenofibrate is a white solid which is stable under ordinary conditions.
Inactive Ingredients: Each tablet contains crospovidone, lactose monohydrate, mannitol, maltodextrin, carboxymethylcellulose sodium, egg lecithin, croscarmellose sodium, sodium lauryl sulfate, colloidal silicon dioxide, magnesium stearate, and monobasic sodium phosphate.
Triglide is indicated as adjunctive therapy to diet:
The tablets are supplied as follows:
NDC 70199-013-30: bottles of 30 tablets. 160 mg, off-white round tablets, debossed “FH 160”.
Only dispense Triglide tablets in the original manufacturer bottle with the original desiccant cap. Do not repackage Triglide tablets into standard amber pharmacy vials.
Store at 20°-25°C (68°-77°F); excursions permitted to 15°-30°C (59°-86°F) [See USP Controlled Room Temperature]. Protect from light and moisture. Store tablets only in the moisture protective container.
Manufactured for: Casper Pharma LLC, East Brunswick, NJ 08816 Manufactured by: SkyePharma Production SAS 38070 Saint-Quentin-Fallavier, France Made in France PIB01330-09 © Casper Pharma LLC. All rights reserved. Revised: May 2024
The following serious adverse reactions are described below and elsewhere in the labeling:
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 rates observed in clinical practice.
The safety of Triglide 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]. Dosages of fenofibrate used in these trials were comparable to Triglide 160 mg per day [see CLINICAL PHARMACOLOGY].
Adverse reactions reported by 2% or more of patients treated with fenofibrate (and greater than placebo) during double-blind, placebo-controlled trials are listed in Table 1. 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% |
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.
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 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 comparable to 134 mg to 200 mg fenofibrate daily.
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 Disorders: Anemia
Gastrointestinal Disorders: Pancreatitis
General Disorder: Asthenia
Hepatobiliary Disorders: Increased total bilirubin, hepatitis, cirrhosis
Immune System Disorders: Anaphylaxis, angioedema
Lipid Disorders: Severely depressed HDL-cholesterol levels
Musculoskeletal Disorders: Myalgia, muscle spasms, rhabdomyolysis, arthralgia
Renal and Urinary Disorders: Acute renal failure
Respiratory Disorders: Interstitial lung disease
Skin and Subcutaneous Tissue Disorders: Photosensitivity reactions.
This may occur in patients who report a prior photosensitivity reaction to ketoprofen.
Table 2: Clinically Important Drug Interactions with Triglide
| 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 Triglide 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 Triglide 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 Triglide. 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 Triglide, there is a risk that an interaction will lead to deterioration of renal function. |
| Intervention: | The benefits and risks of using Triglide 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 resins, administer Triglide at least 1 hour before or 4 to 6 hours after the bile acid resins to avoid impeding its absorption. |
Included as part of the PRECAUTIONS section.
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].
Because of chemical, pharmacological, and clinical similarities between Triglide, pemafibrate, clofibrate, and gemfibrozil, findings in 5 large randomized, placebo-controlled clinical trials with these other fibrate drugs may also apply to Triglide.
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].
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 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.
The Helsinki Heart Study, conducted from 1982 to 1987, was a large (n=4,081) 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 years 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.
Serious drug-induced liver injury (DILI), including liver transplantation and death, has been reported postmarketing with Triglide. 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 Triglide 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 has been associated with increases in serum AST or ALT. The incidence of increases in transaminases may be dose related [see ADVERSE REACTIONS].
Triglide is contraindicated in patients with active liver disease, including those with unexplained persistent liver function abnormalities [see CONTRAINDICATIONS]. Monitor patient’s liver function, including serum ALT, AST, and total bilirubin, at baseline and periodically for the duration of therapy with Triglide. Discontinue Triglide 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 Triglide in these patients if there is no alternative explanation for the liver injury.
Triglide may cause myopathy [muscle pain, tenderness, or weakness associated with elevated creatine kinase (CK)] and rhabdomyolysis.
Risk factors for myopathy include age 65 years or greater, uncontrolled hypothyroidism, renal impairment, and concomitant use with certain other drugs [see DRUG INTERACTION and Uses In Specific Populations].
Data from observational studies indicate that the risk for rhabdomyolysis is increased when fibrates are co-administered with a statin. Avoid concomitant use unless the benefit of further alterations in TG levels is likely to outweigh the increased risk of this drug combination [see DRUG INTERACTIONS and CLINICAL PHARMACOLOGY .
Cases of myopathy, including rhabdomyolysis, have been reported with Triglide co-administered with colchicine. Consider whether the benefit of using colchicine concomitantly with Triglide outweighs the increased risk of myopathy [see DRUG INTERACTIONS].
Discontinue Triglide if markedly elevated CK levels occur or if myopathy is either diagnosed or suspected. Muscle symptoms and CK elevations may resolve if Triglide is discontinued. Temporarily discontinue Triglide in patients experiencing an acute or serious condition at high risk of developing renal failure secondary to rhabdomyolysis (e.g., sepsis; shock; severe hypovolemia; major surgery; trauma; severe metabolic, endocrine, or electrolyte disorders; or uncontrolled epilepsy).
Inform patients of the risk of myopathy and rhabdomyolysis when starting or increasing the Triglide dosage. Instruct patients to promptly report any unexplained muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever.
Increases in serum creatinine have been reported in patients on Triglide. These increases tend to return to baseline following discontinuation of Triglide. The clinical significance of this finding is unknown. Monitor renal function in patients with renal impairment taking Triglide. Renal monitoring should also be considered for patients taking Triglide at risk for renal insufficiency such as the elderly and patients with diabetes. Triglide is not recommended in patients with mild or moderate renal impairment. Triglide is contraindicated in patients with severe renal impairment, including those with end-stage renal disease (ESRD) and those receiving dialysis [see CONTRAINDICATIONS, Use In Specific Populations, and CLINICAL PHARMACOLOGY].
Fenofibrate may increase cholesterol excretion into the bile, leading to cholelithiasis. If cholelithiasis is suspected, gallbladder studies are indicated. Triglide therapy should be discontinued if gallstones are found. Triglide is contraindicated in patients with preexisting gallbladder disease.
Caution should be exercised when anticoagulants are given in conjunction with Triglide because of the potentiation of coumarin-type anti-coagulant effects in prolonging the prothrombin time/International Normalized Ration (PT/INR). 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 [see DRUG INTERACTIONS].
Pancreatitis has been reported in patients taking Triglide. 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.
Mild to moderate hemoglobin, hematocrit, and white blood cell decreases have been observed in patients following initiation of Triglide. However, these levels stabilize during long-term administration. Thrombocytopenia and agranulocytosis have been reported in individuals treated with Triglide. Periodic monitoring of red and white cell counts is recommended during the first 12 months of Triglide administration.
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 Triglide. Triglide is contraindicated in patients with a hypersensitivity to fenofibrate, fenofibric acid, or any of the ingredients in Triglide.
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 Triglide. 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.
In the Fenofibrate Intervention and Event Lowering in Diabetes (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 (1.4%) in the fenofibrate group (p = 0.074); and for PE, there were 32 (0.7%) events in the placebo group and 53 (1.1%) 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).
In the cardiovascular outcome trial with pemafibrate, pulmonary embolism was reported for 37 (0.7%) subjects in the pemafibrate group and 16 (0.3%) subjects in the placebo group. Deep vein thrombosis was reported for 36 (0.7%) subjects in the pemafibrate group and 13 (0.2%) subjects in the placebo group.
There have been postmarketing and clinical trial reports of severe decreases in HDL cholesterol levels (as low as 2 mg/dL) occurring in patients with and without diabetes 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. Check HDL-C levels within the first few months after initiation of Triglide. If a severely depressed HDL-C level is detected, discontinue Triglide and monitor HDL-C until it has returned to baseline. Triglide should not be re-initiated.
Two dietary carcinogenicity studies have been conducted in rats with fenofibrate. In the first 24-month study, Wistar rats were dosed with fenofibrate at 10 mg/kg/day, 45 mg/kg/day and 200 mg/kg/day, approximately 0.3 times, 1 time, and 6 times the maximum recommended human dose (MRHD), based on body surface area comparisons (mg/m²). At a dose of 200 mg/kg/day (at 6 times MRHD), the incidence of liver carcinoma was significantly increased in both sexes. A statistically significant increase in pancreatic carcinomas was observed in males at 1 and 6 times the MRHD; an increase in pancreatic adenomas and benign testicular interstitial cell tumors was observed in males at 6 times the MRHD. In a second 24-month study in a different strain of rats (Sprague-Dawley), doses of 10 mg/kg/day and 60 mg/kg/day (0.3 times and 2 times the MRHD) produced significant increases in the incidence of pancreatic acinar adenomas in both sexes and increases in testicular interstitial cell tumors in males at 2 times the MRHD.
A 117-week carcinogenicity study was conducted in rats comparing three drugs: fenofibrate 10 mg/kg/day and 60 mg/kg/day (0.3 and 2 times the MRHD), clofibrate (400 mg/kg; 2 times the human dose), and gemfibrozil (250 mg/kg; 2 times the human dose, based on mg/m² surface area). Fenofibrate increased pancreatic acinar adenomas in both sexes. Clofibrate increased hepatocellular carcinomas in males and hepatic neoplastic nodules in females. Gemfibrozil increased hepatic neoplastic nodules in males and females, while all three drugs increased testicular interstitial cell tumors in males.
In a 21-month study in CF-1 mice, fenofibrate 10 mg/kg/day, 45 mg/kg/day and 200 mg/kg/day (approximately 0.2 times, 1 time, and 3 times the MRHD on the basis of mg/m² surface area) significantly increased the liver carcinomas in both sexes at 3 times the MRHD. In a second 18-month study at 10 mg/kg/day, 60 mg/kg/day and 200 mg/kg/day, fenofibrate significantly increased the liver carcinomas in male mice and liver adenomas in female mice at 3 times the MRHD.
Electron microscopy studies have demonstrated peroxisomal proliferation following fenofibrate administration to the rat. An adequate study to test for peroxisome proliferation in humans has not been done, but changes in peroxisome morphology and numbers have been observed in humans after treatment with other members of the fibrate class when liver biopsies were compared before and after treatment in the same individual.
Fenofibrate has been demonstrated to be devoid of mutagenic potential in the following tests: Ames, mouse lymphoma, chromosomal aberration and unscheduled DNA synthesis in primary rat hepatocytes.
In fertility studies rats were given oral dietary doses of fenofibrate, males received 61 days prior to mating and females 15 days prior to mating through weaning which resulted in no adverse effect on fertility at doses up to 300 mg/kg/day (approximately 10 times the MRHD, based on mg/m² surface area comparisons).
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 dose of 160 mg daily, based on body surface area (mg/m²). Adverse reproductive outcomes occurred at higher doses in the presence of maternal toxicity [see Data]. Fenofibrate tablets 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.
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 160 mg Triglide 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 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.
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 fenofibrates tablets and for 5 days after the final dose [see CONTRAINDICATIONS].
The safety and effectiveness of Triglide have not been established in pediatric patients with severe hypertriglyceridemia or primary hyperlipidemia.
Assess renal function in elderly patients and follow contraindications and dosing recommendations for patients with renal impairment [see CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS, and Use In Specific Populations]. While fenofibric acid exposure is not influenced by age, elderly patients are more likely to have renal impairment, and fenofibric acid is substantially excreted by the kidney [see CLINICAL PHARMACOLOGY].
Consider monitoring renal function in elderly patients taking Triglide.
Triglide is contraindicated in patients with severe renal impairment (eGFR <30 mL/min), including those with end-stage renal disease (ESRD) and those receiving dialysis [see CONTRAINDICATIONS]. Triglide is not recommended for use in patients with mild or moderate renal impairment (eGFR 30 to <60 mL/min) because these patients require a lower dosage of fenofibrate than what is available for Triglide. 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, and CLINICAL PHARMACOLOGY].
The use of Triglide has not been evaluated in subjects with hepatic impairment. Triglide is contraindicated in patients with active liver disease, including those with unexplained persistent liver function abnormalities [see CONTRAINDICATIONS and CLINICAL PHARMACOLOGY].
In the event of an overdose of Triglide, 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 Triglide. 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 fenofibrate is highly bound to plasma proteins, hemodialysis should not be considered.
Triglide is contraindicated in the following conditions:
The active moiety of Triglide 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, fenofibrate 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).
Fenofibric acid, the active metabolite of fenofibrate, produces reductions in total cholesterol, total triglycerides, and triglyceride rich lipoprotein (VLDL) in treated patients with severe hypertriglyceridemia.
Triglide 160 mg tablet was shown to have comparable bioavailability to a single dose of 200 mg fenofibrate capsule, micronized. Fenofibrate is a pro-drug of the active chemical moiety fenofibric acid. Fenofibrate is converted by ester hydrolysis in the body to fenofibric acid which is the active constituent measurable in the circulation.
The absolute bioavailability of fenofibrate cannot be determined as the compound is virtually insoluble in aqueous media suitable for injection. Fenofibrate is insoluble in water and its bioavailability is optimized when taken with meals. However, after fenofibrate is dissolved, fenofibrate is well absorbed from the gastrointestinal tract. Following oral administration in healthy volunteers, approximately 60% of a single dose of radiolabelled fenofibrate appeared in urine, primarily as fenofibric acid and its glucuronate conjugate, and 25% was excreted in the feces. Peak plasma levels of fenofibric acid occur an average of 3 hours after administration.
Effect Of Food
The extent of absorption of Triglide (AUC) is comparable between fed and fasted conditions. High-fat meal increases the rate of absorption of Triglide approximately 55%.
In healthy volunteers, steady-state plasma levels of fenofibric acid were shown to be achieved within a week of dosing and did not demonstrate accumulation across time following multiple dose administration. Serum protein binding was approximately 99% in normal and hyperlipidemic subjects.
Metabolism
Following oral administration, fenofibrate is rapidly hydrolyzed by esterases to the active metabolite, fenofibric acid; no unchanged fenofibrate is detected in plasma. Fenofibric acid is primarily conjugated with glucuronic acid and then excreted in urine. A small amount of fenofibric acid is reduced at the carbonyl moiety to a benzhydrol metabolite which is, in turn, conjugated with glucuronic acid and excreted in urine. In vivo metabolism data indicate that neither fenofibrate nor fenofibric acid undergo oxidative metabolism (e.g., cytochrome P450) to a significant extent.
Excretion
After absorption, fenofibrate is mainly excreted in the urine in the form of metabolites, primarily fenofibric acid and fenofibric acid glucuronide. After administration of radio-labelled fenofibrate, approximately 60% of the dose appeared in the urine and 25% was excreted in the feces. Fenofibric acid is eliminated with a half-life of approximately 16 hours, allowing once daily dosing.
In elderly volunteers aged 77 to 87 years, the oral clearance of fenofibric acid following a single oral dose of fenofibrate was 1.2 L/h, which compares to 1.1 L/h in young adults. This indicates that a similar dosage regimen can be used in the elderly, without increasing accumulation of the drug or metabolites.
Pharmacokinetics of Triglide has not been studied in pediatric patients.
No pharmacokinetic difference between males and females has been observed for fenofibrate.
The influence of race on the pharmacokinetics of fenofibrate has not been studied; however, fenofibrate is not metabolized by enzymes known for exhibiting inter-ethnic variability.
The pharmacokinetics of fenofibric acid was examined in patients with mild, moderate, and severe renal impairment. Patients with severe renal impairment (creatinine clearance [CrCl ≤30 mL/min] <30 mL/min or estimated glomerular filtration rate [eGFR] <30 mL/min) showed 2.7-fold increase in exposure for fenofibric acid and increased accumulation of fenofibric acid during chronic dosing compared to that of healthy subjects. Patients with mild to moderate renal impairment (CrCl 30 mL/min to 80 mL/min or eGFR 30 mL/min to 59 mL/min) had similar exposure but an increase in the half-life for fenofibric acid compared to that of healthy subjects.
No pharmacokinetic studies have been conducted in patients having hepatic impairment.
In vitro studies using human liver microsomes indicate that fenofibrate and fenofibric acid are not inhibitors of cytochrome (CYP) P450 isoforms CYP3A4, CYP2D6, CYP2E1, or CYP1A2. They are weak inhibitors of CYP2C8, CYP2C19 and CYP2A6, and mild-to-moderate inhibitors of CYP2C9 at therapeutic concentrations.
Table 3 describes the effects of co-administered drugs on fenofibric acid systemic exposure. Table 4 describes the effects of fenofibrate on co-administered drugs.
Table 3: Effects of Co-Administered Drugs on Fenofibric Acid Systemic Exposure from Fenofibrate Administration
| Co-Administered Drug | Dosage Regimen of CoAdministered Drug | Dosage Regimen of Fenofibrate | Changes in Fenofibric Acid Exposure | |
| AUC | Cmax | |||
| Lipid-lowering agents | ||||
| Atorvastatin | 20 mg once daily for 10 days | Fenofibrate 160 mg1 once daily for 10 days | ↓2% | ↓4% |
| Pravastatin | 40 mg as a single dose | Fenofibrate 3 x 67 mg2 as a single dose | ↓1% | ↓2% |
| Fluvastatin | 40 mg as a single dose | Fenofibrate 160 mg1 as a single dose | ↓2% | ↓10% |
| Anti-diabetic agents | ||||
| Glimepiride | 1 mg as a single dose | Fenofibrate 145 mg1 once daily for 10 days | ↑1% | ↓1% |
| Metformin | 850 mg three times daily for 10 days | Fenofibrate 54 mg1 three times daily for 10 days | ↓9% | ↓6% |
| Rosiglitazone | 8 mg once daily for 5 days | Fenofibrate 145 mg1 once daily for 14 days | ↑10% | ↑3% |
| 1 TriCor (fenofibrate) oral tablet 2 TriCor (fenofibrate) oral micronized capsule |
||||
Table 4: Effects of Fenofibrate on Systemic Exposure of Co-Administered Drugs
| Dosage Regimen of Fenofibrate | Dosage Regimen of CoAdministered Drug | Change in Co-Administered Drug Exposure | ||
| Analyte | AUC | Cmax | ||
| Lipid-lowering agents | ||||
| Fenofibrate 160 mg1 once daily for 10 days | Atorvastatin, 20 mg once daily for 10 days | Atorvastatin | ↓17% | 0% |
| Fenofibrate 3 x 67 mg2 as a single dose | Pravastatin, 40 mg as a single dose | Pravastatin | ↑13% | ↑13% |
| 3a-Hydroxyl-iso- pravastatin | ↑26% | ↑29% | ||
| Fenofibrate 160 mg1 as a single dose | Fluvastatin, 40 mg as a single dose | (+)-3R, 5S-Fluvastatin | ↑15% | ↑16% |
| Anti-diabetic agents | ||||
| Fenofibrate 145 mg1 once daily for 10 days | Glimepiride, 1 mg as a single dose | Glimepiride | ↑35% | ↑18% |
| Fenofibrate 54 mg1 three times daily for 10 days | Metformin, 850 mg three times daily for 10 days | Metformin | ↑3% | ↑6% |
| Fenofibrate 145 mg1 once daily for 14 days | Rosiglitazone, 8 mg once daily for 5 days | Rosiglitazone | ↑6% | ↓1% |
| 1 TriCor (fenofibrate) oral tablet 2 TriCor (fenofibrate) oral micronized capsule |
||||
The effectiveness of Triglide 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.” Dosages of fenofibrate used in these trials were comparable to Triglide 160 mg per day [see CLINICAL PHARMACOLOGY].
The effects of fenofibrate on serum triglycerides were studied in two randomized, double-blind, placebo-controlled clinical trials of 147 patients with hypertriglyceridemia. Patients were treated for eight weeks under protocols that differed only in that one entered patients with baseline triglyceride (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 decreased primarily very low-density lipoprotein (VLDL) triglycerides and VLDL cholesterol. Treatment of patients with elevated triglycerides often results in an increase of low-density lipoprotein (LDL) cholesterol (see Table 5).
Table 5: Effects of Fenofibrate in Patients with Hypertriglyceridemia
| Study 1 | Macebo | Fenofibrate** | ||||||
| Baseline TG levels 350 to 499 mg/dL | N | Baseline (Mean) | Endpoint (Mean) | % Change (Mean) | N | Baseline (Mean) | Endpoint (Mean) | % Change (Mean) |
| 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 | 14.5 |
| VLDL Cholesterol | 27 | 99 | 99 | 5.8 | 27 | 92 | 46 | -44.7* |
| Study 2 | Placebo | Fenofibrate** | ||||||
| Baseline TG levels 500 to 1500 mg/dL | N | Baseline (Mean) | Endpoint (Mean) | % Change (Mean) | N | Baseline (Mean) | Endpoint (Mean) | % Change (Mean) |
| Triglycerides | 44 | 710 | 750 | 7.2 | 48 | 726 | 308 | -54.5* |
| Study 1 | Placebo | Fenofibrate** | ||||||
| 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 | 48 | 30 | 36 | 22.9* |
| LDL Cholesterol | 42 | 100 | 90 | -4.2 | 45 | 103 | 131 | 45* |
| VLDL Cholesterol | 42 | 137 | 142 | 11 | 45 | 126 | 54 | -49.4* |
| * =p<0.05 vs. placebo ** Dosage comparable to 160 mg Triglide |
||||||||
The effects of fenofibrate were assessed in four randomized, placebo-controlled, double-blind, parallel-group trials in patients with hyperlipidemia and mixed dyslipidemia. Fenofibrate therapy reduced LDL-C, Total-C, and triglycerides, and increased HDL-C (see Table 6).
Table 6: Mean Percent Change in Lipid Parameters at End of Treatment*
| Treatment Group | Total-C | LDL-C | HDL-C | TG |
| Mean baseline lipid values (n = 646) | 306.9 mg/dL | 213.8 mg/dL | 52.3 mg/dL | 191 mg/dL |
| All fenofibrate (n = 361) | -18.7%† | -20.6%† | +11%† | -28.9%† |
| Placebo (n = 285) | -0.4% | -2.2% | +0.7% | +7.7% |
| * Duration of study treatment was 3 to 6 months. † p=<0.05 vs. placebo |
||||
Fenofibrate did not reduce cardiovascular disease morbidity or mortality in two large, randomized controlled trials of patients with type 2 diabetes mellitus.
The Action to Control Cardiovascular Risk in Diabetes Lipid (ACCORD Lipid) (NCT00000620) trial was a randomized placebo-controlled trial of 5,518 patients (2,765 assigned to receive fenofibrate) with type 2 diabetes mellitus on background statin therapy treated with fenofibrate. The mean age at baseline was 62 years and 31% were female. Overall, 68% were White, 15% were Black or African American; 7% identified as Hispanic or Latino. The mean duration of follow-up was 4.7 years. The primary outcome of major adverse cardiovascular events (MACE), a composite of non-fatal myocardial infarction, non-fatal stroke, and cardiovascular disease death was a HR of 0.92 (95% CI, 0.79 to 1.08) for fenofibrate plus statin combination therapy as compared to statin monotherapy.
The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study was a 5-year randomized, placebo-controlled trial of 9,795 patients (4,895 assigned to receive fenofibrate) with type 2 diabetes mellitus treated with fenofibrate. The mean age at baseline was 62 years, 37% were female, and 93% were White. The primary outcome of coronary heart disease events was a HR of 0.89 (95% CI, 0.75 to 1.05) with fenofibrate compared to placebo. The HR for total and coronary heart disease mortality, respectively, was 1.11 (95% CI, 0.95 to 1.29) and 1.19 (95% CI, 0.90 to 1.57)with fenofibrate as compared to placebo.
Because of chemical, pharmacological, and clinical similarities between fenofibrate and pemafibrate, findings in a large randomized, placebo-controlled clinical trial with pemafibrate are relevant for Triglide.
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 (NCT03071692). The trial was a randomized placebo-controlled trial of 10,497 patients (5,240 assigned to receive pemafibrate) with type 2 diabetes mellitus on background lipid-lowering therapy. The median age at baseline was 64 years and 28% were female. Overall, 86% were White, 5% were Asian, 3% were Black or African American; 19% identified as Hispanic or Latino. The median duration of follow-up was 3.4 years. The primary outcome of major adverse cardiovascular events (MACE), a composite of non-fatal myocardial infarction, non-fatal ischemic stroke, coronary revascularization, and death from cardiovascular causes, was a HR of 1.03 (95% CI, 0.91 to 1.15) for pemafibrate plus statin combination therapy as compared to statin monotherapy.
Inform patients that Triglide 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, WARNINGS AND PRECAUTIONS].
Advise patients that Triglide 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 Triglide. Instruct patients to promptly report any unexplained muscle pain, tenderness, or weakness particularly if accompanied by malaise or fever [see WARNINGS AND PRECAUTIONS and DRUG INTERACTIONS].
Inform patients that serious hypersensitivity reactions, such as anaphylaxis and angioedema, have been reported with fibrates. 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].
Advise patients to inform their healthcare provider of a known or suspected pregnancy to discuss if Triglide should be discontinued [see Use In Specific Populations]. Lactation Advise patients that breastfeeding during treatment with Triglide is not recommended [see Use In Specific Populations].
If a dose is missed, advise patients not take an extra dose and to resume treatment with the next dose.
