fenofibric acid

fenofibric acid

Trilipix

Pharmacologic class: Fibric acid derivative

Therapeutic class: Antihyperlipidemic

Pregnancy risk category C

Action

Increases lipolysis and elimination of triglyceride-rich particles from plasma by activating lipoprotein lipase and reducing production of Apo CII (an inhibitor of lipoprotein lipase activity)

Availability

Capsules (delayed-release): 45 mg, 135 mg

Indications and dosages

Adjunct to diet in combination with a statin in patients with mixed dyslipidemia and coronary heart disease (CHD) or a risk equivalent; adjunct to diet in patients with primary hyperlipidemia or mixed dyslipidemia

Adults: 135 mg P.O. daily

Adjunct to diet in patients with severe hypertriglyceridemia

Adults: 45 to 135 mg P.O. daily

Dosage adjustment

• Mild to moderate renal impairment

Contraindications

• Hypersensitivity to drug, choline fenofibrate, or fenofibrate
• Severe renal impairment, including patients receiving dialysis
• Active liver disease, gallbladder disease
• Breastfeeding

Precautions

Use cautiously in:
• myositis, myopathy
• administration with maximum dosage of a statin (avoid use unless benefit outweighs risk)
• administration with oral anticoagulants
• pregnant patients
• children (safety and efficacy not established).

Administration

• Administer with or without food (but not with large amounts of grapefruit juice) and have patient swallow capsule whole.
• Be aware that drug isn't indicated for patients with elevated chylomicron and plasma triglyceride levels but with normal very-low-density lipoprotein level.

Adverse reactions

CNS: fatigue, dizziness, headache, insomnia

CV: hypertension

EENT: nasopharyngitis, sinusitis, pharyngolaryngeal pain, rhinitis

GI: nausea, constipation, diarrhea, dyspepsia, abdominal pain, pancreatitis

GU: urinary tract infection

Musculoskeletal: back pain, muscle spasms, extremity pain, arthralgia, myalgia, musculoskeletal pain, myositis, myopathy, rhabdomyolysis

Respiratory: upper respiratory tract infection, bronchitis, cough, respiratory disorder

Skin: rash, Stevens-Johnson syndrome, toxic epidermal necrolysis (rare)

Other: pain, influenza, acute hypersensitivity

Interactions

Drug-drug.Bile acid resins: decreased fenofibric acid absorption

Immunosuppressants (such as cyclosporine): increased risk of nephrotoxicity

Oral anticoagulants: prolonged prothrombin time or International Normalized Ratio

Drug-diagnostic tests.Alanine aminotransferase (ALT), aspartate aminotransferase, creatine kinase (CK), hepatic enzymes, serum creatinine: elevated levels

Hematocrit, hemoglobin, WBC: decreased levels

Drug-food.Grapefruit juice (more than 1 qt daily): increased risk of myopathy when fenofibric acid is taken with statins

Drug-behaviors.Alcohol use (excessive): exacerbation of hypertriglyceridemia

Patient monitoring

Monitor CK level; discontinue drug if markedly elevated CK level occurs or myopathy or myositis is diagnosed.

Regularly monitor liver function tests, including serum ALT; discontinue drug if levels persist above three times upper limit of normal.

Be aware that drug may increase cholesterol excretion into bile, potentially leading to cholelithiasis. Discontinue drug if gallstones develop.
• Monitor serum lipid levels periodically.
• Monitor renal function tests closely in patients at risk for renal insufficiency, such as elderly patients and those with diabetes mellitus.

Patient teaching

• Instruct patient to take drug with or without food (but not with large amounts of grapefruit juice) and to swallow capsule whole.
• Instruct patient that if drug is prescribed with another cholesterol-lowering drug called a statin, these drugs should be taken together.

Instruct patient to promptly inform prescriber if unexplained muscle pain, tenderness, or weakness occurs, particularly if accompanied by malaise or fever.

Instruct patient to promptly inform prescriber if skin blistering, peeling, or loosening; red lesions; severe rash; fever; or chills occur because these signs and symptoms may signal a serious skin disorder.
• Advise patient not to take other prescription or nonprescription drugs or herbal or vitamin supplements without first discussing with prescriber.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, foods, and behaviors mentioned above.

fenofibric acid

(feen-ohfye-brik as-id) ,

Fibricor

(trade name),

TriLipix

(trade name)

Classification

Therapeutic: lipid lowering agents
Pharmacologic: fibric acid derivatives

Indications

With a statin to reduce triglycerides (TG) and increase high density lipoprotein-C (HDL-C) in patients with mixed dyslipidemias and CHD or a CHD risk equivalent who are on statin therapy to achieve their low-density lipoprotein-C (LDL-C) goal (TriLipix only).As monotherapy to reduce TG in patients with severe hypertriglyceridemia.As monotherapy to reduce elevated LDL-C, total cholesterol (Total-C), TG and apolipoprotein B (Apo B), and increase HDL-C in patients with primary hyperlipidemia or mixed dyslipidemia.Part of a comprehensive program to decrease cardiovascular risk factors.

Action

Activates the peroxisome proliferator activated receptor α (PPARα), resulting in increased lipolysis and elimination of triglycerides from plasma. Activation of PPARα also increases production of HDL.

Therapeutic effects

Improvement in lipid profile with lowered triglycerides and LDL cholesterol, and increased HDL cholesterol.

Pharmacokinetics

Absorption: Well absorbed following oral administration.
Distribution: Unknown.
Protein Binding: 99%.
Metabolism and Excretion: Fenofibric acid is the active metabolite of fenofibrate. Fenofibric acid is mostly metabolized by glucuronidation and the metabolites are mostly excreted by the kidneys.
Half-life: 20 hr.

Time/action profile (effects on blood lipids)

ROUTEONSETPEAKDURATION
POunknown4–5 hr†unknown
†Blood levels

Contraindications/Precautions

Contraindicated in: Hypersensitivity to fenofibric acid, choline fenofibrate or fenofibrate;Severe renal impairment (CCr <30 mL/min);Active liver or gallbladder disease; Lactation: Avoid use during breast feeding.
Use Cautiously in: Mild/moderate renal impairment (dose ↓ required for CCr 30–80 mL/min);Concurrent use with statins in elderly patients, patients with diabetes, renal failure, or hypothyroidism (↑ risk of myopathy/rhabdomyolysis); Geriatric: Consider age-related ↓ in renal function, concurrent illnesses and drug therapy; Obstetric: Use only if the potential benefit justifies the potential risk to the fetus; Pediatric: Safety and effectiveness not established.

Adverse Reactions/Side Effects

Central nervous system

  • headache (most frequent)

Gastrointestinal

  • diarrhea (most frequent)
  • nausea (most frequent)
  • cholelithiasis
  • ↑ liver enzymes
  • pancreatitis

Genitourinary

  • ↑ serum creatinine

Metabolic

  • ↓ HDL levels

Musculoskeletal

  • myopathy/rhabdomyolysis (life-threatening)
  • myalgia (most frequent)
  • back pain

Interactions

Drug-Drug interaction

↑ effects and risk of bleeding with warfarin ; monitor prothrombin time/INR.Bile acid sequestrants may ↓ absorption and effectiveness; administer at least 1 hr before or 4–6 hr after a bile acid sequestrant.Concurrent use with nephrotoxic drugs including cyclosporine may impair renal function and excretion, ↑ risk of adverse reactions.Concurrent use with colchicine may ↑ risk of rhabdomyolysis

Route/Dosage

Mixed Dyslipidemia

Oral (Adults) TriLipix—135 mg once daily; Hypertriglyceridemia—45–135 mg once daily.

Hypertriglyceridemia

Oral (Adults) Fibricor—35–105 mg once daily; TriLipix—45–135 mg once daily.

Primary Hypercholesterolemia or Mixed Dyslipidemia

Oral (Adults) Fibricor—105 mg once daily; TriLipix—135 mg once daily.

Renal Impairment

Oral (Adults) CCr 30–80 mL/min—Fibricor: Initiate with 35 mg once daily; may titrate cautiously; TriLipix: Initiate with 45 mg once daily; may titrate cautiously; CCr <30 mL/min—Contraindicated.

Availability (generic available)

Delayed-release capsules (Fibricor): 35 mg, 105 mg
Delayed-release capsules (TriLipix): 45 mg, 135 mg

Nursing implications

Nursing assessment

  • Obtain a diet history, especially with regard to fat consumption. Every attempt should be made to obtain normal serum triglyceride levels with diet, exercise, and weight loss in obese patients before fenofibric acid therapy is instituted.
  • Assess patient for cholelithiasis. If symptoms occur, gallbladder studies are indicated. Discontinue therapy if gallstones are found.
  • Lab Test Considerations: Monitor serum lipids before therapy to determine consistent elevations, then monitor periodically during therapy.
    • Monitor serum AST and ALT periodically during therapy. May cause ↑ levels. Discontinue therapy if levels rise >3 times the normal limit.
    • If patient develops muscle tenderness during therapy, CPK levels should be monitored. If CPK levels are markedly ↑ or myopathy occurs, therapy should be discontinued.
    • May cause reversible ↑ in serum creatinine. Monitor renal function in patients at risk for renal insufficiency (elderly, diabetics).
    • May cause mild to moderate ↓ in hemoglobin, hematocrit, and WBCs. Monitor periodically during first 12 mo of therapy. Levels usually stabilize during long-term therapy.
    • Monitor prothrombin time and INR monitored frequently until levels stabilize in patients taking anticoagulants concurrently.

Potential Nursing Diagnoses

Noncompliance (Patient/Family Teaching)

Implementation

  • Patients should be placed on a triglyceride-lowering diet before therapy and remain on this diet throughout therapy.
  • Oral: Administer without regard to meals. Swallow capsules whole; do not open, crush, or chew. May be administered at same time as statin dose.

Patient/Family Teaching

  • Instruct patient to take medication as directed. Take missed doses as soon as remembered; if time for next dose, skip dose and take next dose at regular time. Do not double doses. Medication helps control but does not cure elevated serum triglyceride levels. Advise patient to read Medication Guide before starting and with each Rx refill, as new information may be available.
  • Advise patient that this medication should be used in conjunction with diet restrictions (fat, cholesterol, carbohydrates, alcohol), exercise, and cessation of smoking.
  • Instruct patient to notify health care professional if unexplained muscle pain, tenderness, weakness, tiredness, fever, nausea, vomiting, or abdominal pain occurs, especially if accompanied by fever or malaise.
  • Instruct female patients to notify health care professional promptly if pregnancy is planned or suspected.
  • Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
  • Advise patient to notify health care professional of medication regimen before treatment or surgery.
  • Emphasize the importance of follow-up exams to determine effectiveness and to monitor for side effects.

Evaluation/Desired Outcomes

  • Decrease in serum triglycerides and LDL cholesterol to normal levels with an increase in HDL levels.
Mentioned in ?
References in periodicals archive ?
Food and Drug Administration for its Abbreviated New Drug Application for fenofibric acid EQ 45 mg and EQ 135 mg delayed-release (DR) capsules.
Members of a Food and Drug Administration advisory panel were divided on whether the approved indication for fenofibric acid, when co-administered with a statin, should be revised based on trial results showing no benefit of the drug in reducing cardiovascular disease risk when added to a stain in patients with type 2 diabetes.
The next day, we placed the cells in serum-free DMEM treated with 200[micro]mol/L fenofibric acid (ABCR GmbH) dissolved in dimethyl sulfoxide (Sigma).
This entrenchment means that agents in other anti-dyslipidemic drug classes such as Abbott's fenofibrate (Tricor), fenofibric acid (TriLipix), extended-release niacin (Niaspan), omega-3-acid ethyl ester (Lovaza), and Merck's ezetimibe (Zetia) and ezetimibe/simvastatin (Vytorin) have faced an uphill struggle to gain significant traction in this market.
has launched Fenofibric Acid Delayed-release Capsules, 45 mg and 135 mg.
The approval is based on the results of three phase III studies involving more than 2,600 patients with mixed lipidemia, which showed that when used in combination with a statin, fenofibric acid improved all three key lipids better than a statin alone.
Fenofibric acid reduces triglyceride levels and increases high-density lipoprotein cholesterol levels, so the combination targets three key lipid parameters and addresses mixed dyslipidemia more effectively than any other current or emerging therapy.
Food and Drug Administration (FDA) issued a complete response letter (CRL) for the New Drug Application (NDA) for CERTRIAD(TM) (rosuvastatin / fenofibric acid delayed release) Capsules.
The NDA submission is supported by data from multiple studies, including efficacy and safety studies with the 5 mg, 10 mg and 20 mg doses of rosuvastatin combined with fenofibric acid.
The NDA submission for this investigational compound, containing the active ingredients of CRESTOR(R) (rosuvastatin calcium) and TRILIPIX(R) (fenofibric acid), is supported by data from multiple studies, including efficacy and safety studies with the 5mg, 10mg and 20mg doses of rosuvastatin combined with fenofibric acid.
Presented TRILIPIX(TM) / CRESTOR(R) Combination Data at ACC: A new study of Abbott's fenofibric acid, TRILIPIX, used in combination with the lowest available dose of CRESTOR (5 mg) showed that the combination led to greater improvements in all three lipids - LDL, HDL and triglycerides - than the corresponding monotherapies.
TriLipix is an investigational new fenofibric acid molecule, currently in clinical development for treating patients with unhealthy lipid levels, including LDL cholesterol, triglycerides and HDL cholesterol.