FENOGET Capsule

Treatment of Hypercholesterolemia

FENOGET is 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).

Treatment of Hypertriglyceridemia

FENOGET is indicated as adjunctive therapy to diet for treatment of adult patients with hypertriglyceridemia (Fredrickson Types Ⅳand Ⅴhyperlipidemia).

Dosage and Administration

Patients should be placed on an appropriate lipid-lowering diet before receiving FENOGET capsules and should continue on this diet during treatment.

FENOGET capsules should be given with meals, thereby optimizing the bioavailability of the medication.

Primary hypercholesterolemia or mixed hyperlipidemia:

For the treatment of adult patients with primary hypercholesterolemia or mixed hyperlipidemia, the initial dose of FENOGET capsules is 200mg per day.

Hypertriglyceridemia

For adult patients with hypertriglyceridemia, the initial dose is 67-200mg per day. Dosage should be individualized according to patient response, and should be adjusted if necessary following repeat lipid determinations at 4-8 week intervals. The maximum dose is 200mg per day.

See the package insert about the details below:

- Renal Insufficient Patients

- Elderly

In patients

- With hypersensitivity to fenofibrate or any of the formulation components.

- With severe renal dysfunction.

- With hepatic dysfunction, including primary biliary cirrhosis and unexplained persistent liver function abnormality.

- Pre-existing gall bladder disease.

Fenofibrate should not be used in nursing mothers.

The most common adverse reactions reported with fenofibrate therapy were gastrointestinal (diarrhea, constipation, dyspepsia, flatulence), muscle pain, and skin reactions.

There is a slightly increased risk of gallstones, inflamed liver (hepatitis), and muscle inflammation (myositis).

Other adverse effects include:

Headache, fatigue, muscle inflammation, inflammation of the pancreas (pancreatitis), balance problems involving the inner ear (vertigo), respiratory problems, muscle breakdown (rhabdomyolysis), hair loss (alopecia), alteration in results of liver function tests, sexual problems.

See the package insert about the details below:

- Oral Anticoagulants

- HMG-CoA Reductase Inhibitors (Statins)

- Resins

- Cyclosporine

- Beta-blockers, thiazides, estrogens

Pregnancy

There are no adequate and well-controlled studies in pregnant women. Fenofibrate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

- Initial Therapy: Laboratory studies should be done to ascertain that the lipid levels are consistently abnormal before instituting therapy with fenofibrate. Every attempt should be made to control serum lipids with appropriate diet, exercise, weight loss in abese patients, and control of any medical problems such as diabetes mellitus and hypothyroidism that are contributing to the lipid abnormalities.

- Continued Therapy: Periodic determination of serum lipids should be obtained to determine the lowest effective dose of fenofibrate. Therapy should be withdrawn in patients who do not have an adequate response after two months of treatment with the maximum recommended dose.

- Fenofibrate therapy is not indicated for patients with TypeⅠhyperlipoproteinemia, who have elevations of chylomicrons and plasma triglycerides, but who have normal levels of very low-density lipoprotein (VLDL).

- Regular periodic monitoring of liver function, including serum ALT (SGPT) should be performed for the duration of therapy with fenofibrate, and therapy should be discontinued if enzyme levels persist above 3 times the normal limit.

- Fenofibrate, like clofibrate and gemfibrozil, may increase cholesterol excretion into the bile, leading to cholelithiasis. If cholelithiasis is suspected, gall bladder studies are indicated and fenofibrate therapy should be discontinued if gallstones are found.

- Periodic blood counts are recommended during the first 12 months of fenofibrate administration.

- Patients receiving fenofibrate and complaining of muscle pain, tenderness, or weakness should have prompt medical evaluation for myopathy, including serum creatinine kinase level determination. If myopathy/myositis is suspected or diagnosed, fenofibrate therapy should be stopped.

Fenofibrate is a fibric acid derivative whose lipid modifying effects reported in humans are mediated via activation of Peroxisome Proliferator Activated Receptor type alpha (PPARα). Through activation of PPARα, fenofibrate increases the lipolysis and elimination of atherogenic triglyceride-rich particles from plasma by activating lipoprotein lipase and reducing production of apoprotein CⅢ. Activation of PPARαalso induces an increase in the synthesis of apoproteins AⅠand AⅡ.

The above stated effects of fenofibrate on lipoproteins lead to a reduction in very low- and low density fractions (VLDL and LDL) containing apoprotein B and an increase in the high density lipoprotein fraction (HDL) containing apoprotein AⅠand AⅡ. In addition, through modulation of the synthesis and the catabolism of VLDL fractions fenofibrate increases the LDL clearance and reduces small dense LDL, the levels of which are elevated in the atherogenic lipoprotein phenotype, a common disorder in patients at risk for coronary heart disease.