Ezetimibe: uses, appearance and warnings

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). As an adjunct to diet for the reduction of elevated sitosterol and campesterol levels in adults and in pediatric patients 9 years of age and older with homozygous familial sitosterolemia. When ZETIA is used in combination with a statin, fenofibrate, or other LDL-C lowering therapies, refer to the Prescribing Information of these products for information on the safe and effective use. ZETIA is indicated ( 1 ): 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). As an adjunct to diet for the reduction of elevated sitosterol and campesterol levels in adults and in pediatric patients 9 years of age and older with homozygous familial sitosterolemia. When ZETIA is used in combination with a statin, fenofibrate, or other LDL-C lowering therapies, refer to the Prescribing Information of these products for information on the safe and effective use ( 1 ).

Tablets: 10-mg white to off-white, capsule-shaped, and debossed with "414" on one side. Tablets: 10 mg ( 3 )

ZETIA 10 mg tablets are white to off-white, capsule-shaped, and debossed with "414" on one side and are supplied as follows: Package Size NDC Bottle of 30 tablets 78206-178-01 Store ZETIA at room temperature between 68°F to 77°F (20°C to 25°C). Protect from moisture.

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 [see Adverse Reactions (6.2) ] . 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 [see Warnings and Precautions (5.1) ] . Hypersensitivity to ezetimibe or any excipient of ZETIA. ( 4 ) 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. ( 4 )

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. ( 5.1 ) 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. ( 5.2 ) 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. ( 5.3 ) 5.1 Risks Associated with Combination Treatment with a Statin, Fenofibrate, or Other LDL-C Lowering Therapies If ZETIA is administered 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 [see Contraindications (4) ] . 5.2 Liver Enzymes Increases in serum transaminases have been reported with use of ZETIA [see Adverse Reactions (6.1) ] . In controlled clinical combination studies of ZETIA initiated concurrently with a statin, the incidence of consecutive elevations (≥3 × ULN) in hepatic transaminase levels was 1.3% for patients treated with ZETIA administered with statins and 0.4% for patients treated with statins alone. Perform liver enzyme testing as clinically indicated and consider withdrawal of ZETIA if increases in ALT or AST ≥3 × ULN persist. 5.3 Myopathy/Rhabdomyolysis ZETIA may cause myopathy [muscle pain, tenderness, or weakness associated with elevated creatine kinase (CK)] and rhabdomyolysis [see Adverse Reactions (6.1) ] . 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 [see Warnings and Precautions (5.2) ] Rhabdomyolysis and myopathy [see Warnings and Precautions (5.3) ] 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. ( 6.1 ) 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. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Organon LLC, a subsidiary of Organon & Co., at 1-844-674-3200 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . …

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 [see Clinical Pharmacology (12.3) ] . 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. …