Fenofibrate

Article Author:
Gursharan Sidhu
Article Editor:
Jayson Tripp
Updated:
6/25/2020 12:44:29 PM
PubMed Link:
Fenofibrate

Indications

Fenofibrate is FDA approved for the management and treatment of hypertriglyceridemia, primary hypercholesterolemia or mixed dyslipidemia. It reduces low-density lipoprotein, triglycerides, and total cholesterol while increasing high-density lipoprotein cholesterol in adults. Fenofibrate should be used in conjunction with a restriction of cholesterol intake and exercise if lifestyle modifications alone have been insufficient. The clinician needs to rule out hyperlipidemia or dyslipidemia due to secondary causes before initiating treatment. The medication is safe and effective for use in the geriatric population. However, drug safety and efficacy are unestablished in the pediatrics population. Fenobrifate may be used in pregnancy if the potential benefits outweigh the potential risk to the fetus. Off-label fenofibrate may be used as adjunctive therapy for elevated blood uric acid levels in individuals with gout.[1][2]

Mechanism of Action

Fibrates such as fenofibrate activate peroxisome proliferator-activated receptors alpha (PPAR-alpha), which upregulate lipoprotein lipase, induce high-density lipoprotein (HDL) synthesis, and decrease liver production of apolipoprotein C. Fibrates ultimately enhance the clearance of triglyceride-rich particles and plasma catabolism. Fibrates also enhance fatty acid oxidation via acyl CoA synthetase and other enzymes, which further reduce the synthesis of triglycerides. The end result is an overall reduction of plasma triglyceride and very-low-density lipoprotein (VLDL) levels. The decrease in VLDL can cause plasma triglyceride levels to decrease by 30% to 60%. Fenofibrate may facilitate an increase in uric acid excretion and reduction of fibrinogen, which may help patients with gout and thrombosis. 

Fenofibrate has a bioavailability of between 60 to 90% and a half-life of 20 hours. It is metabolized via the hepatic pathway and eliminated through urine.[3][4][5]

Administration

Fenofibrate capsules and tablets are administered orally once daily with or without food. The capsules should be swallowed whole and should not be crushed, dissolved, or chewed. Fenofibrate therapy may be considered as an option in individuals taking moderate-intensity statin therapy if the benefits (i.e., decreasing cardiovascular disease risk) outweigh the potential risks of adverse effects. Dose adjustments are made on 4 to 8-week intervals based on individual response.[6]

Hypertriglyceridemia, primary hypercholesterolemia or mixed dyslipidemia:

In adults and geriatrics population do not exceed:

  • 145 mg PO daily for Tricor brand tablets
  • 160 mg PO daily for Triglide brand tablets
  • 200 mg PO daily for Lofibra brand capsules
  • 90 mg PO daily for Antara brand capsules
  • 150 mg PO daily for Lipofen brand capsules

Patients with hepatic impairment should avoid the use of fenofibrate. In patients with renal impairment, no dose adjustment is necessary if creatinine clearance is above 80 mL/min. Fenofibrate is contraindicated if creatinine clearance is under 30mL/min or if the patient has severe renal dysfunction. 

Adverse Effects

Some of the most common adverse effects associated with fibrates include headache, dizziness, back pain, joint pain, diarrhea, dyspepsia, cough, wheezing, nasopharyngitis, and flu-like symptoms. Some potentially serious adverse effects that may require dose adjustment or discontinuation may include elevated liver enzymes, elevated creatine phosphokinase (CPK), cholelithiasis development, arrhythmia exacerbation, pulmonary embolism, pancreatitis, agranulocytosis, and myocardial infarction.[7][8]

Contraindications

Fenofibrate is contraindicated for patients with a history of hypersensitivity to fenofibrate, liver disease, severe renal dysfunction, preexisting gallbladder disease, or breastfeeding. Fenofibrate may also interact with other drugs and may require a change in dose, frequency, or switching to a new therapy. When prescribing fenofibrate in conjunction with statins (HMG-CoA reductase inhibitors) or colchicine, rhabdomyolysis and myopathy may occur. There is also an increased incidence of myopathy related to fenofibrate therapy in patients diagnosed with diabetes mellitus, thyroid disorder, or a renal disorder. 

Fibrates, especially gemfibrozil, are associated with an increased risk of cholecystitis and cholelithiasis due to their ability to increase the saturation of cholesterol in bile. Patients with severe renal dysfunction, including those on dialysis, should avoid fenofibrate due to reduced drug clearance and increased risk of myositis. Caution is necessary if patients are on anticoagulation therapy as fenofibrate may potentiate the effects of coumarin-type medications.[9][10][11]

Monitoring

Patients on fenofibrate should undergo monitoring for the effectiveness of treating a medical condition and any adverse effects pertaining to the medication. A complete list of patient medications should be reviewed prior to initiating drug therapy. The clinician should discontinue treatment if an inadequate response is not seen within 2 to 3 months of beginning the fenofibrate therapy. Kidney function labs such as uric acid (UA), blood urea nitrogen (BUN), and creatine clearance (CrCl) should have regular monitoring in individuals with renal impairment, and dosing should be adjusted as needed. The hepatic function is crucial to monitor to avoid administering the medication to individuals with an active hepatic disorder or persistently elevated serum transaminases. Regular monitoring of creatine phosphokinase (CPK) levels is a requirement to check for any signs and symptoms of myopathy or rhabdomyolysis. Blood counts should also be periodically monitored to reduce risks of thrombocytopenia and agranulocytosis. A periodic lipid panel, including total cholesterol, HDL, LDL, and triglyceride levels, should be conducted to assess for drug safety and efficacy.  

Fenofibrate should be stored in a cool place away from light and moisture.[12][13]

Toxicity

The most common toxicity associated with fenofibrate is myopathy when given with a statin concurrently. If rhabdomyolysis is excluded and other muscle-related diseases are suspected, the statin-associated muscle symptoms clinical index (SAMS-CI) should undergo an evaluation to determine if muscle symptoms are due to statin therapy. Discontinuing the use of fenofibrate, administering vitamin D replacement (for low vitamin D levels), and switching the medication are all possible options depending on the cause of myopathy.[14]

Enhancing Healthcare Team Outcomes

A team of interdisciplinary professionals is the optimal approach for the management of fenofibrate involving primary care providers, nurses, and pharmacists. Medical professionals should be aware of the signs and symptoms that accompany fenofibrate toxicity. The involvement of other specialized professionals, including a nephrologist or toxicologist, should be considered to ensure an optimal patient result. Clinicians must counsel patients regarding any symptoms associated with liver damage (weakness, weight change, abdominal pain, jaundice).

Pharmacists should actively monitor for drug interactions before distributing medication and must notify the medical provider of any issues. The medical care provider should advise the patient on the importance of reading labels pertaining to the medication to avoid drug misuse or overdose. An interactive team dynamic for fenofibrate therapy is essential in managing any adverse effects and providing successful patient care for an optimal therapeutic outcome.  


References

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