Ezetimibe

ZETIA ® is indicated: In combination with a statin, or alone when additional low-density lipoprotein cholesterol (LDL-C) lowering therapy is not possible, as an adjunct to diet to reduce elevated LDL-C in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH). In combination with a statin as an adjunct to diet to reduce elevated LDL-C in pediatric patients 10 years of age and older with HeFH. In combination with fenofibrate as an adjunct to diet to reduce elevated LDL-C in adults with mixed hyperlipidemia. In combination with a statin, and other LDL-C lowering therapies, to reduce elevated LDL-C levels in adults and in pediatric patients 10 years of age and older with homozygous familial hypercholesterolemia (HoFH).

Ezetimibe reduces blood cholesterol by inhibiting the absorption of cholesterol by the small intestine. 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 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 LDL receptors, resulting in clearance of cholesterol from the blood.

The recommended dose of ZETIA is 10 mg orally once daily, administered with or without food. If as dose is missed, take the missed dose as soon as possible. Do not double the next dose. Assess LDL-C when clinically appropriate, as early as 4 weeks after initiating ZETIA. Administer ZETIA at least 2 hours before or 4 hours after administration of a bile acid sequestrant. 10-mg orally once daily, with or without food. Administer ZETIA either ≥2 hours before or ≥4 hours after administration of a bile acid sequestrant.

ZETIA is contraindicated in patients with a known hypersensitivity to ezetimibe or any of the excipients in ZETIA. Hypersensitivity reactions including anaphylaxis, angioedema, rash, and urticaria have been reported. When used in combination with a statin, fenofibrate, or other LDL-C lowering therapy, ZETIA is contraindicated in patients for whom a statin, fenofibrate, or other LDL-C lowering therapy are contraindicated. Refer to the Prescribing Information of these products for a list of their contraindications. Hypersensitivity to ezetimibe or any excipient of ZETIA.

Risks Associated with Combination Treatment with a Statin, Fenofibrate, or Other LDL-C Lowering Therapies: Refer to the Prescribing Information of these products for a description of their risks including, but not limited to, the warnings and precautions. Liver Enzyme Abnormalities and Monitoring: Increases in serum transaminases have been reported with use of ZETIA. Perform liver enzyme testing as clinically indicated and consider withdrawal of ZETIA if increases in ALT or AST ≥3 × ULN persist. Skeletal Muscle Effects (e.g., Myopathy and Rhabdomyolysis): ZETIA may cause myopathy and rhabdomyolysis. In post-marketing reports, most patients who developed rhabdomyolysis were taking a statin or other agents known to be associated with an increased risk of rhabdomyolysis, such as fibrates. If myopathy is suspected, discontinue ZETIA and other concomitant medications, as appropriate.

The following serious adverse reactions are discussed in greater detail in other sections of the label: Liver enzyme abnormalities Rhabdomyolysis and myopathy Common adverse reactions in clinical trials: ZETIA administered alone (incidence ≥2% and greater than placebo): upper respiratory tract infection, diarrhea, arthralgia, sinusitis, pain in extremity, fatigue, and influenza. ZETIA coadministered with a statin (incidence ≥2% and greater than statin alone): nasopharyngitis, myalgia, upper respiratory tract infection, arthralgia, diarrhea, back pain, influenza, pain in extremity, and fatigue.

Table 3 includes a list of drugs with clinically important drug interactions when administered concomitantly with ZETIA and instructions for preventing or managing them. Table 3: Clinically Important Drug Interactions with ZETIA Cyclosporine Clinical Impact: Concomitant use of ZETIA and cyclosporine increases ezetimibe and cyclosporine concentrations. The degree of increase in ezetimibe exposure may be greater in patients with severe renal insufficiency. Intervention: Monitor cyclosporine concentrations in patients receiving ZETIA and cyclosporine. In patients treated with cyclosporine, weigh the potential effects of the increased exposure to ezetimibe from concomitant use against the benefits of alterations in lipid levels provided by ZETIA. Fibrates Clinical Impact: Both fenofibrate and ezetimibe may increase cholesterol excretion into the bile, leading to cholelithiasis.

Store ZETIA at room temperature between 68°F to 77°F (20°C to 25°C). Protect from moisture.