ADVERSE REACTIONS

ZETIA has been evaluated for safety in more than 4700 patients in clinical trials. Clinical studies of ZETIA (administered alone or with an HMG-CoA reductase inhibitor) demonstrated that ZETIA was generally well tolerated. The overall incidence of adverse events reported with ZETIA was similar to that reported with placebo, and the discontinuation rate due to adverse events was also similar for ZETIA and placebo.

Monotherapy

Adverse experiences reported in 2% of patients treated with ZETIA and at an incidence greater than placebo in placebo-controlled studies of ZETIA, regardless of causality assessment, are shown in Table 8.

The frequency of less common adverse events was comparable between ZETIA and placebo.

Combination with an HMG-CoA reductase Inhibitor

ZETIA has been evaluated for safety in combination studies in more than 2000 patients. In general, adverse experiences were similar between ZETIA administered with HMG-CoA reductase inhibitors and HMG-CoA reductase inhibitors alone. However, the frequency of increased transaminases was slightly higher in patients receiving ZETIA administered with HMG-CoA reductase inhibitors than in patients treated with HMG-CoA reductase inhibitors alone. (See PRECAUTIONS, Liver Enzymes.) Clinical adverse experiences reported in 2% of patients and at an incidence greater than placebo in four placebo-controlled trials where ZETIA was administered alone or initiated concurrently with various

HMG-CoA reductase inhibitors, regardless of causality assessment, are shown in Table 9.

Post-marketing Experience

The following adverse reactions have been reported in post-marketing experience: Hypersensitivity reactions, including angioedema and rash.