Fenofibric Acid
FDA Drug Information • Also known as: Fenofibric Acid, Fenofibric Acid Delayed-Release
- Brand Names
- Fenofibric Acid, Fenofibric Acid Delayed-Release
- Dosage Form
- CAPSULE, DELAYED RELEASE
- Product Type
- DRUG FOR FURTHER PROCESSING
Description
11 DESCRIPTION Fenofibric acid delayed-release capsules are a peroxisome proliferator-activated receptor (PPAR) alpha agonist available as delayed release capsules for oral administration. Fenofibric acid delayed-release capsules are a lipid regulating agent available as delayed release capsules for oral administration. Each delayed release capsule contains choline fenofibrate, equivalent to 45 mg or 135 mg of fenofibric acid. The chemical name for choline fenofibrate is ethanaminium, 2-hydroxy-N,N,N-trimethyl, 2-{4-(4-chlorobenzoyl)phenoxy] -2-methylpropanoate (1:1) with the following structural formula: The empirical formula is C 22 H 28 ClNO 5 and the molecular weight is 421.91. Choline fenofibrate is freely soluble in water and methanol. The melting point is approximately 210°C. Choline fenofibrate is a white to off-white crystalline powder, which is stable under ordinary conditions. Each delayed release capsule contains enteric coated mini-tablets comprised of choline fenofibrate and the following inactive ingredients: colloidal silicon dioxide, hydroxylpropyl cellulose, hypromellose, methacrylic acid copolymer, povidone, sodium stearyl fumarate, talc, triethyl citrate, water. The capsule shell of the 45 mg capsule contains the following inactive ingredients: gelatin, iron oxide red, iron oxide yellow and titanium dioxide. The capsule shell of the 135 mg capsule contains the following inactive ingredients: FD&C Blue #2, gelatin, iron oxide yellow and titanium dioxide. The capsule shells are printed with edible black ink and white ink. The edible white ink contains potassium hydroxide, propylene glycol, shellac and titanium dioxide and the edible black ink contains iron oxide black, potassium hydroxide, propylene glycol and shellac. structure
What Is Fenofibric Acid Used For?
1 INDICATIONS AND USAGE Fenofibric acid delayed-release capsules indicated as adjunctive therapy to diet:
Dosage and Administration
2 DOSAGE AND ADMINISTRATION Severe hypertriglyceridemia: 45 to 135 mg orally once daily; the dosage should be adjusted according to patient response (2.2). Primary hyperlipidemia: 135 mg orally once daily (2.2). Administer as a single dose, at any time of day, with or without food (2.2). Assess TG when clinically appropriate, as early as 4 to 8 weeks after initiating fenofibric acid delayed-release capsules. Discontinue fenofibric acid delayed-release capsules in patients who do not have an adequate response after 2 months of treatment (2.2). Swallow capsules whole. Do not crush, break, dissolve, or chew (2.2). Renal impairment: Initial dosage of 45 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 Fenofibric Acid Delayed-Release Capsules
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS 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 Alembic Pharmaceuticals Limited at 1-866-210-9797 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 fenofibric acid delayed-release capsules 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 fenofibric acid delayed-release capsules 135 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. 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 three 12-week, double-blind, controlled studies of fenofibric acid delayed-release capsules, increases in ALT and AST > 3 times the upper limit of normal on two consecutive occasions occurred in 1.9% and 0.2%, respectively, of patients receiving fenofibric acid delayed-release capsules 135 mg daily and placebo, without other lipid-altering drugs. 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 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]. Clinical trials with fenofibric acid delayed-release capsules did not include a placebo-control arm. However, the...
Drug Interactions
7 DRUG INTERACTIONS Table 2 presents clinically important drug interactions with fenofibric acid delayed-release capsules. Table 2. Clinically Important Drug Interactions with Fenofibric Acid Delayed-Release Capsules 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 fenofibric acid delayed-release capsules 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 fenofibric acid delayed-release capsules 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 fenofibric acid delayed-release capsules. 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 fenofibric acid delayed-release capsules, there is a risk that an interaction will lead to deterioration of renal function. Intervention: The benefits and risks of using fenofibric acid delayed-release capsules with immunosuppressants and other potentially nephrotoxic agents should be carefully considered, and the lowest effective 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 fenofibric acid delayed-release capsules 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...
Contraindications
4 CONTRAINDICATIONS Fenofibric acid delayed-release capsules are 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 fenofibric acid, fenofibrate, or any of the excipients in fenofibric acid delayed-release capsules. 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 fenofibric acid, fenofibrate, or any of the excipients in fenofibric acid delayed-release capsules (4).
Pregnancy and Breastfeeding
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 135 mg of fenofibric acid delayed-release capsules daily, based on body surface area (mg/m 2 ). Adverse reproductive outcomes occurred at higher doses in the presence of maternal toxicity (see Data). Fenofibric acid delayed-release capsules 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 135 mg fenofibric acid delayed-release capsule 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...
Overdosage
10 OVERDOSAGE In the event of an overdose of fenofibric acid delayed-release capsules, 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 fenofibric acid delayed-release capsules. General supportive care of the patient is indicated, including monitoring of vital signs and observation of clinical status, should an overdose occur. If indicated, elimination of unabsorbed drug should be achieved by emesis or gastric lavage; usual precautions should be observed to maintain the airway. Because fenofibric acid delayed-release capsules are highly bound to plasma proteins, hemodialysis should not be considered.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING Fenofibric acid delayed-release capsules 45 mg have a brown opaque cap/ yellow opaque body size ‘3’ hard gelatin capsule imprinted with ‘A’ on the cap in white ink and ‘138’ on the body in black ink, filled with white to off white mini tablets. NDC 62332-244-30 30 Capsules HDPE Bottle Pack NDC 62332-244-90 90 Capsules HDPE Bottle Pack NDC 62332-244-91 1000 Capsules HDPE Bottle Pack Fenofibric acid delayed-release capsules 135 mg have a blue opaque cap/ yellow opaque body size ‘0’ hard gelatin capsule imprinted with ‘A’ on the cap in white ink and ‘139’ on the body in black ink, filled with white to off white mini tablets. NDC 62332-245-30 30 Capsules HDPE Bottle Pack NDC 62332-245-90 90 Capsules HDPE Bottle Pack NDC 62332-245-91 1000 Capsules HDPE Bottle Pack Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Keep out of the reach of children. Protect from moisture.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.