Description:
EZEGO (Ezetimibe) is in a class of lipid-lowering compounds that selectively inhibits the intestinal absorption of cholesterol and related phytosterols. The chemical name of ezetimibe is 1-(4-fluorophenyl)- 3(R)-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4(S)-(4-hydroxyphenyl)-2-azetidinone. The empirical formula is C24H21F2NO3. Its molecular weight is 409.4.

Pharmacodynamics:
Ezetimibe has a mechanism of action that differs from those of other classes of cholesterol-reducing compounds (HMG-CoA reductase inhibitors, bile acid sequestrants [resins], fibric acid derivatives, and plant stanols). The molecular target of ezetimibe has been shown to be the sterol transporter, Niemann- Pick C1-Like 1 (NPC1L1), which is involved in the intestinal uptake of cholesterol and phytosterols.
Ezetimibe does not inhibit cholesterol synthesis in the liver, or increase bile acid excretion. Instead, ezetimibe localizes at the brush border of the small intestine and inhibits the absorption of cholesterol, leading to a decrease in the delivery of intestinal cholesterol to the liver. This causes a reduction of hepatic cholesterol stores and an increase in clearance of cholesterol from the blood; this distinct mechanism is complementary to that of HMG-CoA reductase inhibitors and of fenofibrate.

Effect of Food on Oral Absorption:
Concomitant food administration (high fat or non-fat meals) had no effect on the extent of absorption of ezetimibe when administered as EZEGO (Ezetimibe) 10 mg tablet. The Cmax value of ezetimibe was increased by 38% with consumption of high fat meals. EZEGO (Ezetimibe) can be administered with or without food.
Distribution:
Ezetimibe and ezetimibe-glucuronide are highly bound (>90%) to human plasma proteins.
Metabolism and Excretion:
Ezetimibe is primarily metabolized in the small intestine and liver via glucuronide conjugation (a phase II reaction) with subsequent biliary and renal excretion. Minimal oxidative metabolism (a phase I reaction) has been observed in all species evaluated.
Elimination:
Exetimibe is mainly excreated through the feces and urine.

Indication and Usage:
Primary Hypercholesterolemia
Monotherapy
EZEGO (Ezetimibe), administered alone, is indicated as adjunctive therapy to diet for the reduction of elevated total-C, LDL-C, and Apo B in patients with primary (heterozygous familial and non-familial) hypercholesterolemia.
Combination Therapy with HMG-CoA Reductase Inhibitors
EZEGO (Ezetimibe), administered in combination with an HMG-CoA reductase inhibitor, is indicated as adjunctive therapy to diet for the reduction of elevated total-C, LDL-C, and Apo B in patients with primary (heterozygous familial and non-familial) hypercholesterolemia.
Combination Therapy with Fenofibrate:
EZEGO (Ezetimibe), administered in combination with fenofibrate, is indicated as adjunctive therapy to diet for the reduction of elevated total-C, LDL-C, Apo B, and non-HDL-C in patients with mixed hyperlipidemia.
Homozygous Familial Hypercholesterolemia (HoFH)
The combination of EZEGO (Ezetimibe) and atorvastatin or simvastatin, is indicated for the reduction of elevated total-C and LDL-C levels in patients with HoFH, as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) or if such treatments are unavailable.
Homozygous Sitosterolemia:
EZEGO (Ezetimibe) is indicated as adjunctive therapy to diet for the reduction of elevated sitosterol and campesterol levels in patients with homozygous familial sitosterolemia.

Dosage and Administration:
The patient should be placed on a standard cholesterol-lowering diet before receiving EZEGO (Ezetimibe) and should continue on this diet during treatment with EZEGO (Ezetimibe). The recommended dose of EZEGO (Ezetimibe) is 10 mg once daily. EZEGO (Ezetimibe) can be administered with or without food.

Contraindications:
Hypersensitivity to any component of this medication. The combination of EZEGO (Ezetimibe) with an HMG-CoA reductase inhibitor is contraindicated in patients with active liver disease or unexplained persistent elevations in serum transaminases.

Precautions:
Concurrent administration of EZEGO (Ezetimibe) with a specific HMG-CoA reductase inhibitor or fenofibrate should be in accordance with the product labeling for that medication.

Hepatic Insufficiency:
Due to the unknown effects of the increased exposure to ezetimibe in patients with moderate or severe hepatic insufficiency, EZEGO (Ezetimibe) is not recommended in these patients.

Renal Insufficiency:
No dosage adjustment is necessary in patients with renal insufficiency

Drug Interactions
Cholestyramine: Concomitant cholestyramine administration decreases the mean AUC of total ezetimibe approximately 55%. The incremental LDL-C reduction due to adding ezetimibe to cholestyramine may be reduced by this interaction.
Fibrates: The co-administration of ezetimibe with fibrates other than fenofibrate has not been studied. Fibrates may increase cholesterol excretion into the bile, leading to cholelithiasis.
Fenofibrate: In a pharmacokinetic study, concomitant fenofibrate administration increased total ezetimibe concentrations approximately 1.5-fold.
HMG-CoA Reductase Inhibitors: No clinically significant pharmacokinetic interactions were seen when ezetimibe was co-administered with atorvastatin, simvastatin, pravastatin, lovastatin, fluvastatin, or rosuvastatin.
Cyclosporine: Caution should be exercised when using EZEGO (Ezetimibe) and cyclosporine concomitantly due to increased exposure to both ezetimibe and cyclosporine. Cyclosporine concentrations should be monitored in patients receiving EZEGO (Ezetimibe) and cyclosporine.
The degree of increase in ezetimibe exposure may be greater in patients with severe renal insufficiency. In patients treated with cyclosporine, the potential effects of the increased exposure to ezetimibe from concomitant use should be carefully weighed against the benefits of alterations in lipid levels provided by ezetimibe.
Warfarin: If ezetimibe is added to warfarin, the International Normalized Ratio should be appropriately monitored.

Pregnancy and Lactation
Pregnancy
Pregnancy Category: C
There are no adequate and well-controlled studies of ezetimibe in pregnant women. Ezetimibe should be used during pregnancy only if the potential benefit justifies the risk to the fetus.
Nursing Mothers
It is not known whether ezetimibe is excreted into human breast milk; therefore, EZEGO (Ezetimibe) should not be used in nursing mothers unless the potential benefit justifies the potential risk to the infant.

Overdosage:
Generally well tolerated. In the event of an overdose, symptomatic and supportive measures should be employed.

Storage:
Store below 30ºC.
Protect from light, heat and moisture.
Keep all medicines out of the reach of children.