INDICATIONS AND USAGE

ZETIA® is an inhibitor of intestinal cholesterol (and related phytosterol) absorption indicated as an adjunct to diet to:

• Reduce elevated total-C, LDL-C, and Apo B in patients with primary hyperlipidemia, alone or in combination with an HMG-CoA reductase inhibitor (statin) (1.1)
• Reduce elevated total-C, LDL-C, Apo B, and non-HDL-C in patients with mixed hyperlipidemia in combination with fenofibrate (1.1)
• Reduce elevated total-C and LDL-C in patients with homozygous familial hypercholesterolemia (HoFH), in combination with atorvastatin or simvastatin (1.2)
• Reduce elevated sitosterol and campesterol in patients with homozygous sitosterolemia (phytosterolemia) (1.3)

Limitations of Use (1.4)

• The effect of ZETIA on cardiovascular morbidity and mortality has not been determined.
• ZETIA has not been studied in Fredrickson Type I, III, IV, and V dyslipidemias.

DOSAGE AND ADMINISTRATION

• One 10-mg tablet once daily, with or without food (2.1)
• Dosing of ZETIA should occur either ≥2 hours before or ≥4 hours after administration of a bile acid sequestrant. (2.3, 7.4)

DOSAGE FORMS AND STRENGTHS

• Tablets: 10 mg (3)

CONTRAINDICATIONS

• Statin contraindications apply when ZETIA is used with a statin:
  • Active liver disease, which may include unexplained persistent elevations in hepatic transaminase levels (4, 5.2)
  • Women who are pregnant or may become pregnant (4, 8.1)
  • Nursing mothers (4, 8.3)
• Known hypersensitivity to product components (4, 6.2)

WARNINGS AND PRECAUTIONS

• ZETIA is not recommended in patients with moderate or severe hepatic impairment. (5.4, 8.6, 12.3)
• Liver enzyme abnormalities and monitoring: Persistent elevations in hepatic transaminase can occur when ZETIA is added to a statin. Therefore, when ZETIA is added to statin therapy, monitor hepatic transaminase levels before and during treatment according to the recommendations for the individual statin used. (5.2)
• Skeletal muscle effects (e.g., myopathy and rhabdomyolysis):
  • Cases of myopathy and rhabdomyolysis have been reported in patients treated with ZETIA co-administered with a statin and with ZETIA administered alone. Risk for skeletal muscle toxicity increases with higher doses of statin, advanced age (>65), hypothyroidism, renal impairment, and depending on the statin used, concomitant use of other drugs. (5.3, 6.2)

ADVERSE REACTIONS

• Common adverse reactions in clinical trials:
  • ZETIA co-administered with a statin (incidence ≥2% and greater than statin alone):
    • nasopharyngitis, myalgia, upper respiratory tract infection, arthralgia, and diarrhea (6)
  • ZETIA administered alone (incidence ≥2% and greater than placebo):
    • upper respiratory tract infection, diarrhea, arthralgia, sinusitis, and pain in extremity (6)
  
  

  To report SUSPECTED ADVERSE REACTIONS, contact Merck/Schering-Plough Pharmaceuticals at 1-866-637-2501 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS

• Cyclosporine: Combination increases exposure of ZETIA and cyclosporine. Cyclosporine concentrations should be monitored in patients taking ZETIA concomitantly. (7.1, 12.3)
• Fenofibrate: Combination increases exposure of ZETIA. If cholelithiasis is suspected in a patient receiving ZETIA and fenofibrate, gallbladder studies are indicated and alternative lipid-lowering therapy should be considered. (6.1, 7.3)
• Fibrates: Co-administration of ZETIA with fibrates other than fenofibrate is not recommended until use in patients is adequately studied. (7.2)
• Cholestyramine: Combination decreases exposure of ZETIA. (2.3, 7.4, 12.3)

1 INDICATIONS AND USAGE

1.1 Primary Hyperlipidemia

1.2 Homozygous Familial Hypercholesterolemia (HoFH)

1.3 Homozygous Sitosterolemia

1.4 Limitations of Use

2 DOSAGE AND ADMINISTRATION

2.1 General Dosing Information

2.2 Concomitant Lipid-Lowering Therapy

2.3 Co-Administration with Bile Acid Sequestrants

2.4 Patients with Hepatic Impairment

2.5 Patients with Renal Impairment

2.6 Geriatric Patients

3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

5 WARNINGS AND PRECAUTIONS