Fenofibrate

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[edit] BRAND NAMES

[edit] STRUCTURE

Fenofibrate.jpg

[edit] MECHANISM OF ACTION

Fenofibrate is an oral antilipemic agent. It is a fibric acid derivative; other members of this drug class include clofibrate bezafibrate, ciprofibrate and gemfibrozil.

Fibrates exert their effects mainly by activating the peroxisome proliferator-activated receptor-alpha (PPARα) system that regulates lipid metabolism.

Through this mechanism, fibrates increase 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).

Activation of PPARα also induces an increase in the synthesis of apoproteins A-I, A-II and HDL-cholesterol.

Fibrates have been shown to reduce plasma triglycerides (TG) by 30% to 50% and raise the level of high density lipoprotein cholesterol (HDL-C) by 2% to 20%. Their effect on low density lipoprotein cholesterol (LDL-C) is variable, ranging from no effect to a small decrease of the order of 10%. That's why they are mainly used when help is needed to bring down triglycerides.


The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) on 28 February 2011 has concluded that fibrates (except fenofibrate) should not be used as first-line treatment in patients with high lipid levels, except in specific groups:

  • patients with severe hypertriglyceridaemia;
  • patients for whom statins are contraindicated or who cannot tolerate them.

The Committee allowed the use of fenofibrate together with a statin in some circumstances for patients at risk when using a statin on its own was not enough to completely control blood lipid levels.

[edit] INDICATIONS

Fenofibrate is indicated as an adjunct to diet and other non-pharmacological treatment (e.g. exercise, weight reduction) for the following:

  • Primary hypercholesterolemia or mixed dyslipidemia (elevated LDL-cholesterol and triglyceride). (U.S.)
  • Mixed hyperlipidemia (elevated LDL-cholesterol and triglyceride) when a statin is contraindicated or not tolerated (Europe)
  • Mixed hyperlipidemia (elevated LDL-cholesterol and triglyceride) in patients at high cardiovascular risk in addition to a statin when triglycerides and HDL cholesterol are not adequately controlled.
  • Hypertriglyceridemia. (U.S.)
  • Severe hypertriglyceridemia with or without low HDL cholesterol (Europe)

[edit] DOSAGE

Fenofibrate nanonised particle size:

  • Hypercholesterolemia or mixed dyslipidemia: 120-150 mg per day
  • Severe hypertriglyceridemia: 40 to 150 mg per day; the dose should be adjusted according to patient response

[edit] CONTRAINDICATIONS

  • Severe renal dysfunction, including patients receiving dialysis
  • Active liver disease
  • Gallbladder disease
  • Nursing mothers
  • Known hypersensitivity to fenofibrate

[edit] WARNINGS AND PRECAUTIONS

  • Myopathy and rhabdomyolysis: Fibrates (with a significantly higher rate observed for gemfibrozil) increase the risk for myopathy and have been associated with rhabdomyolysis. The risk for serious muscle toxicity appears to be increased in elderly patients and in patients with diabetes, renal insufficiency, hypothyroidism, and when co-administered with an HMG-CoA reductase inhibitor (statins). Whilst on treatment, patients should be asked to report inexplicable muscle pain, weakness or cramps immediately, particularly if associated with malaise or fever. Creatine Kinase levels should be measured in these patients. Therapy should be discontinued if Creatine Kinase levels are markedly elevated.
    Cases of myopathy, including rhabdomyolysis, have been reported with fenofibrates co-administered with colchicine, and caution should be exercis ed when prescribing fenofibrate with colchicine
  • Fenofibrate can increase serum transaminases. Monitor liver tests ,including ALT, periodically during therapy.
  • Fenofibrate can reversibly increase serum creatinine levels. Monitor renal function periodically in patients with renal impairment.
  • Fenofibrate, like clofibrate and gemfibrozil, may increase cholesterol excretion into the bile, leading to cholelithiasis. If cholelithiasis is suspected, gallbladder studies are indicated, and therapy should be discontinued if gallstones are found.
  • Exercise caution in concomitant treatment with coumarin anticoagulants (e.g. Warfarin) because of the potentiation of coumarin-type anticoagulants in prolonging the prothrombin time/International Normalized Ratio (PT/INR). Adjust the dosage of coumarin to maintain the prothrombin time/INR at the desired level to prevent bleeding complications.

[edit] INTERACTIONS

  • Coumarin anticoagulants (e.g. Warfarin): Fenofibrate may warrant monitoring for increases in INR/prothrombin time.
  • Immunosuppressants (e.g. cyclosporine and tacrolimus): May decrease renal elimination of fenofibrate.
  • Bile acid sequestrants (e.g. Cholestyramine, Colestipol): May interfere with fenofibrate absorption. Take Fenofibrate at least 1 hour before or 4 to 6 hours after a bile acid binding resin to avoid impeding its absorption
  • Colchicine: Cases of myopathy, including rhabdomyolysis, have been reported with fenofibrates co-administered with colchicine, and caution should be exercised when prescribing fenofibrate with colchicine

[edit] PREGNANCY AND LACTATION

  • Pregnancy Category C (US). Fenofibrate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
  • Nursing Mothers: Fenofibrate should not be used in nursing mothers. A decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

[edit] SIDE EFFECTS

The most common adverse reactions are raised levels of various liver enzymes(AST and ALT), increased creatine phosphokinase (CPK), stomach pain, nausea, diarrhea, flatulence and rhinitis.

[edit] RELATED LINKS

[edit] REFERENCES