Get your patient on Fenofibrate - Fenofibrate capsule (Fenofibrate)
Fenofibrate - Fenofibrate capsule prescribing information
INDICATIONS AND USAGE
Treatment of Hypercholesterolemia
Fenofibrate capsules, USP are indicated as adjunctive therapy to diet for the reduction of LDL-C, Total-C, Triglycerides and apo B in adult patients with primary hypercholesterolemia or mixed dyslipidemia (Fredrickson Types IIa and IIb). Lipid altering agents should be used in addition to a diet restricted in saturated fat and cholesterol when response to diet and non-pharmacological interventions alone has been inadequate (see National Cholesterol Education Program [NCEP] Treatment Guidelines, below).
Treatment of Hypertriglyceridemia
Fenofibrate capsules, USP are also indicated as adjunctive therapy to diet for treatment of adult patients with hypertriglyceridemia (Fredrickson Types IV and V hyperlipidemia). Improving glycemic control in diabetic patients showing fasting chylomicronemia will usually reduce fasting triglycerides and eliminate chylomicronemia thereby obviating the need for pharmacologic intervention.
Markedly elevated levels of serum triglycerides (e.g. > 2,000 mg/dL) may increase the risk of developing pancreatitis. The effect of fenofibrate therapy on reducing this risk has not been adequately studied.
Drug therapy is not indicated for patients with Type I hyperlipoproteinemia, who have elevations of chylomicrons and plasma triglycerides, but who have normal levels of very low density lipoprotein (VLDL). Inspection of plasma refrigerated for 14 hours is helpful in distinguishing Types I, IV and V hyperlipoproteinemia2.
The initial treatment for dyslipidemia is dietary therapy specific for the type of lipoprotein abnormality. Excess body weight and excess alcoholic intake may be important factors in hypertriglyceridemia and should be addressed prior to any drug therapy. Physical exercise can be an important ancillary measure. Diseases contributory to hyperlipidemia, such as hypothyroidism or diabetes mellitus should be looked for and adequately treated. Estrogen therapy, like thiazide diuretics and beta-blockers, is sometimes associated with massive rises in plasma triglycerides, especially in subjects with familial hypertriglyceridemia. In such cases, discontinuation of the specific etiologic agent may obviate the need for specific drug therapy of hypertriglyceridemia.
The use of drugs should be considered only when reasonable attempts have been made to obtain satisfactory results with non-drug methods. If the decision is made to use drugs, the patient should be instructed that this does not reduce the importance of adhering to diet (See WARNINGS and PRECAUTIONS ).
| Type | Lipoprotein Elevated | Lipid Elevation | |
|---|---|---|---|
| Major | Minor | ||
| C = cholesterol TG = triglycerides LDL = low density lipoprotein VLDL = very low density lipoprotein IDL = intermediate density lipoprotein | |||
| I (rare) | Chylomicrons | TG | ↑↔C |
| IIa | LDL | C | — |
| IIb | LDL, VLDL | C | TG |
| III (rare) | IDL | C, TG | — |
| IV | VLDL | TG | ↑↔C |
| V (rare) | Chylomicrons, VLDL | TG | ↑↔ |
| Definite Athlerosclerotic Disease• | Two or More Other Risk Factors† | LDL-Cholesterol mg/dL (mmol/L) | |
|---|---|---|---|
| Initiation Level | Goal | ||
| No | No | ≥ 190 (≥ 4.9) | < 160 (< 4.1) |
| No | Yes | ≥ 160 (≥ 4.1) | < 130 (< 3.4) |
| Yes | Yes or No | ≥ 130‡ (≥ 3.4) | < 100 (< 2.6) |
DOSAGE AND ADMINISTRATION
Patients should be placed on an appropriate lipid-lowering diet before receiving fenofibrate capsules, and should continue this diet during treatment with fenofibrate capsules. Fenofibrate capsules should be given with meals, thereby optimizing the bioavailability of the medication.
For the treatment of adult patients with primary hypercholesterolemia or mixed hyperlipidemia, the initial dose of fenofibrate capsules is 200 mg per day.
For adult patients with hypertriglyceridemia, the initial dose is 67 mg to 200 mg per day.
Dosage should be individualized according to patient response, and should be adjusted if necessary following repeat lipid determinations at 4 to 8 week intervals. The maximum dose is 200 mg per day.
Treatment with fenofibrate capsules, should be initiated at a dose of 67 mg/day in patients having impaired renal function, and increased only after evaluation of the effects on renal function and lipid levels at this dose. In the elderly, the initial dose should likewise be limited to 67 mg/day.
Lipid levels should be monitored periodically and consideration should be given to reducing the dosage of fenofibrate capsules if lipid levels fall significantly below the targeted range.
CONTRAINDICATIONS
Fenofibrate capsules are contraindicated in patients who exhibit hypersensitivity to fenofibrate.
Fenofibrate capsules are contraindicated in patients with hepatic or severe renal dysfunction, including primary biliary cirrhosis, and patients with unexplained persistent liver function abnormality.
Fenofibrate capsules are contraindicated in patients with preexisting gallbladder disease (see WARNINGS).
ADVERSE REACTIONS
Photosensitivity reactions have occurred days to months after initiation; in some of these cases, patients reported a prior photosensitivity reaction to ketoprofen.
Clinical Trials Experience
Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.
Adverse events reported by 2% or more of patients treated with fenofibrate (and greater than placebo) during the double-blind, placebo-controlled trials, regardless of causality, are listed in Table 3 below. Adverse events led to discontinuation of treatment in 5.0% of patients treated with fenofibrate and in 3.0% treated with placebo. Increases in liver function tests were the most frequent events, causing discontinuation of fenofibrate treatment in 1.6% of patients in double-blind trials.
Table 3. Adverse Reactions Reported by 2% or More of Patients Treated withFenofibrate and Greater than Placebo During the Double-Blind, Placebo-Controlled Trials
| BODY SYSTEM Adverse Reaction | Fenofibrate• (N=439) | PLACEBO (N=365) |
|---|---|---|
| BODY AS A WHOLE | ||
| Abdominal Pain | 4.6% | 4.4% |
| Back Pain | 3.4% | 2.5% |
| Headache | 3.2% | 2.7% |
| DIGESTIVE | ||
| Abnormal Liver Function Tests | 7.5%† | 1.4% |
| Nausea | 2.3% | 1.9% |
| Constipation | 2.1% | 1.4% |
| METABOLIC AND NUTRITIONAL DISORDERS | ||
| Increased ALT | 3% | 1.6% |
| Increased CPK | 3% | 1.4% |
| Increased AST | 3.4%† | 0.5% |
| RESPIRATORY | ||
| Respiratory Disorder | 6.2% | 5.5% |
| Rhinitis | 2.3% | 1.1% |
Post-Marketing Experience
The following adverse reactions have been identified during post-approval use of fenofibrate: myalgia, rhabdomyolysis, pancreatitis, acute renal failure, muscle spasm, hepatitis, cirrhosis, anemia, arthralgia, decreases in hemoglobin, decreases in hematocrit, white blood cell decreases and asthenia. 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.
Drug Interactions
Oral Anticoagulants
CAUTION SHOULD BE EXERCISED WHEN COUMARIN ANTICOAGULANTS ARE GIVEN IN CONJUNCTION WITH FENOFIBRATE CAPSULES. THE DOSAGE OF THE ANTICOAGULANTS SHOULD BE REDUCED TO MAINTAIN THE PROTHROMBIN TIME/INR AT THE DESIRED LEVEL TO PREVENT BLEEDING COMPLICATIONS. FREQUENT PROTHROMBIN TIME/INR DETERMINATIONS ARE ADVISABLE UNTIL IT HAS BEEN DEFINITELY DETERMINED THAT THE PROTHROMBIN TIME/INR HAS STABILIZED.
HMG-CoA Reductase Inhibitors
The combined use of fenofibrate and HMG-CoA reductase inhibitors should be avoided unless the benefit of further alterations in lipid levels is likely to outweigh the increased risk of this drug combination (see WARNINGS).
Resins
Since bile acid sequestrants may bind other drugs given concurrently, patients should take fenofibrate capsules at least 1 hour before or 4 to 6 hours after a bile acid binding resin to avoid impeding its absorption.
Cyclosporine
Because cyclosporine can produce nephrotoxicity with decreases in creatinine clearance and rises in serum creatinine, and because renal excretion is the primary elimination route of fibrate drugs including fenofibrate, there is a risk that an interaction will lead to deterioration. The benefits and risks of using fenofibrate with immunosuppressants and other potentially nephrotoxic agents should be carefully considered, and the lowest effective dose employed.
DESCRIPTION
Fenofibrate capsules, USP (micronized) are a lipid regulating agent available as capsules for oral administration. 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.
Each 67 mg fenofibrate capsule, USP contains the following inactive ingredients: sodium lauryl sulfate, croscarmellose sodium, pregelatinized starch, microcrystalline cellulose, colloidal silicon dioxide, sodium stearyl fumarate, titanium dioxide and gelatin. The capsule shell imprinting ink contains the following inactive ingredients: shellac, black iron oxide and potassium hydroxide.
Each 134 mg fenofibrate capsule, USP contains the following inactive ingredients: sodium lauryl sulfate, croscarmellose sodium, pregelatinized starch, microcrystalline cellulose, colloidal silicon dioxide, sodium stearyl fumarate, titanium dioxide, FD&C Yellow 6, D&C Yellow 10 and gelatin. The capsule shell imprinting ink contains the following inactive ingredients: shellac, black iron oxide and potassium hydroxide.
Each 200 mg fenofibrate capsule, USP contains the following inactive ingredients: sodium lauryl sulfate, croscarmellose sodium, pregelatinized starch, microcrystalline cellulose, colloidal silicon dioxide, sodium stearyl fumarate, titanium dioxide, FD&C Yellow 6, D&C Yellow 10 and gelatin. The capsule shell imprinting ink contains the following inactive ingredients: shellac, black iron oxide and potassium hydroxide.
CLINICAL PHARMACOLOGY
A variety of clinical studies have demonstrated that elevated levels of total cholesterol (total-C), low density lipoprotein cholesterol (LDL-C), and apolipoprotein B (apo B), an LDL membrane complex, are associated with human atherosclerosis. Similarly, decreased levels of high density lipoprotein cholesterol (HDL-C) and its transport complex, apolipoprotein A (apo AI and apo AII) are associated with the development of atherosclerosis. Epidemiologic investigations have established that cardiovascular morbidity and mortality vary directly with the level of total-C, LDL-C, and triglycerides, and inversely with the level of HDL-C. The independent effect of raising HDL-C or lowering triglycerides (TG) on the risk of cardiovascular morbidity and mortality has not been determined.
Fenofibric acid, the active metabolite of fenofibrate, produces reductions in total cholesterol, LDL cholesterol, apolipoprotein B, total triglycerides and triglyceride rich lipoprotein (VLDL) in treated patients. In addition, treatment with fenofibrate results in increases in high density lipoprotein (HDL) and apoproteins apo AI and apo AII.
The effects of fenofibric acid seen in clinical practice have been explained in vivo in transgenic mice and in vitro in human hepatocyte cultures by the activation of peroxisome proliferator activated receptor α (PPARα). Through this mechanism, fenofibrate increases lipolysis and elimination of triglyceride-rich particles from plasma by activating lipoprotein lipase and reducing production of apoproteins C-III (an inhibitor of lipoprotein lipase activity). The resulting fall in triglycerides produces an alteration in the size and composition of LDL from small, dense particles (which are thought to be atherogenic due to their susceptibility to oxidation), to large buoyant particles. These larger particles have a greater affinity for cholesterol receptors and are catabolized rapidly. Activation of PPARα also induces an increase in the synthesis of apoproteins A-I, A-II and HDL-cholesterol.
Fenofibrate also reduces serum uric acid levels in hyperuricemic and normal individuals by increasing the urinary excretion of uric acid.
HOW SUPPLIED
Fenofibrate capsules, USP (micronized) 67 mg are opaque white cap and body, hard gelatin capsules, printed in black ink “CL” and “22” on opposing cap and body portions of the capsule. They are supplied as follows:
NDC 35561-345-11 Bottles of 90 capsules
NDC 35561-345-12 Bottles of 100 capsules
Fenofibrate capsules, USP (micronized) 134 mg are opaque white cap and opaque yellow body, hard gelatin capsules, printed in black ink “CL” and “23” on opposing cap and body portions of the capsule. They are supplied as follows:
NDC 35561-346-11 Bottles of 90 capsules
NDC 35561-346-12 Bottles of 100 capsules
Fenofibrate capsules, USP (micronized) 200 mg are opaque yellow cap and body, hard gelatin capsules, printed in black ink “CL” and “24” on opposing cap and body portions of the capsule. They are supplied as follows:
NDC 35561-347-11 Bottles of 90 capsules
NDC 35561-347-12 Bottles of 100 capsules
STORAGE
Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Keep out of the reach of children. Protect from moisture. Dispense in tight, light-resistant container as defined in USP with a child-resistant closure (as required).
