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.
Table 8 *
Clinical Adverse Events Occurring in >/=2% of Patients
Treated with ZETIA and at an Incidence Greater than Placebo, Regardless of Causality
Body System/Organ Class
Adverse Event
|
Placebo
(%)
n = 795
|
ZETIA 10 mg
(%)
n = 1691
|
| Body as a whole - general disorders |
|
Fatigue
|
1.8
|
2.2
|
| Gastro-intestinal system disorders |
|
Abdominal pain
|
2.8
|
3.0
|
|
Diarrhea
|
3.0
|
3.7
|
| Infection and infestations |
|
Infection viral
|
1.8
|
2.2
|
|
Pharyngitis
|
2.1
|
2.3
|
|
Sinusitis
|
2.8
|
3.6
|
| Musculo-skeletal system disorders |
|
Arthralgia
|
3.4
|
3.8
|
|
Back pain
|
3.9
|
4.1
|
| Respiratory system disorders |
|
Coughing
|
2.1
|
2.3
|
|
*Includes patients who received placebo or ZETIA alone reported in Table 9.
|
|
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.
Table 9 *
Clinical Adverse Events occurring in >/=2% of Patients and at an Incidence Greater than Placebo, Regardless of Causality, in ZETIA/Statin Combination Studies
Body System/Organ Class
Adverse Event
|
Placebo
(%)
n=259
|
ZETIA
10 mg
(%)
n=262
|
All Statins **
(%)
n=936
|
ZETIA +
All Statins **
(%)
n=925
|
| Body as a whole - general disorders |
|
Chest pain
|
1.2
|
3.4
|
2.0
|
1.8
|
|
Dizziness
|
1.2
|
2.7
|
1.4
|
1.8
|
|
Fatigue
|
1.9
|
1.9
|
1.4
|
2.8
|
|
Headache
|
5.4
|
8.0
|
7.3
|
6.3
|
| Gastrointestinal system disorders |
|
Abdominal pain
|
2.3
|
2.7
|
3.1
|
3.5
|
|
Diarrhea
|
1.5
|
3.4
|
2.9
|
2.8
|
| Infection and infestations |
|
Pharyngitis
|
1.9
|
3.1
|
2.5
|
2.3
|
|
Sinusitis
|
1.9
|
4.6
|
3.6
|
3.5
|
|
Upper respiratory tract infection
|
10.8 |
13.0 |
13.6 |
11.8 |
| Musculo-skeletal system disorders |
|
Arthralgia
|
2.3
|
3.8
|
4.3
|
3.4
|
|
Back pain
|
3.5
|
3.4
|
3.7
|
4.3
|
|
Myalgia
|
4.6
|
5.0
|
4.1
|
4.5
|
|
*Includes four placebo-controlled combination studies in which ZETIA was initiated concurrently with an HMG-CoA reductase inhibitor.
|
|
**All Statins = all doses of all HMG-CoA reductase inhibitors.
|
|
Post-marketing Experience
The following adverse reactions have been reported in post-marketing experience, regardless of causality assessment:
Hypersensitivity reactions, including angioedema and rash; pancreatitis; nausea; cholelithiasis; cholecystitis.
|
