linically normal dogs in a dose-dependent fashion at a dose that produced plasma drug levels about 30 times higher than the mean drug level in humans taking the highest recommended dose.
6 ADVERSE REACTIONS
The following serious adverse reactions are discussed in greater detail in other sections of the label:
Rhabdomyolysis and myopathy [see Warnings and Precautions (5.1)]
Liver enzyme abnormalities [see Warnings and Precautions (5.2)]
6.1 Clinical Trials Experience
LIPTRUZET
Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in clinical practice.
In a LIPTRUZET (ezetimibe and atorvastatin) placebo-controlled clinical trial, 628 patients (age range 18-86 years, 59% women, 85% Caucasians, 6% Blacks, 5% Hispanics, 3% Asians) with a median treatment duration of 12 weeks, 6% of patients on LIPTRUZET and 5% of patients on placebo discontinued due to adverse reactions.
The most common adverse reactions in the group treated with LIPTRUZET that led to treatment discontinuation and occurred at a rate greater than placebo were:
Myalgia (0.8%)
Abdominal pain (0.8%)
Increased hepatic enzymes (0.8%)
The most commonly reported adverse reactions (incidence ≥2% and greater than placebo) in this trial were: increased ALT (5%), increased AST (4%), and musculoskeletal pain (4%).
LIPTRUZET has been eva luated for safety in 2403 patients in 7 clinical trials (one placebo-controlled trial and six active-controlled trials).
Table 2 summarizes the frequency of clinical adverse reactions reported in ≥2% of patients treated with LIPTRUZET (n=255) and at an incidence greater than placebo, regardless of causality assessment, from the placebo-controlled trial.
Table 2*: Clinical and Selected Laboratory Adverse Reactions Occurring in ≥2% of Patients Treated with LIPTRUZET and at an Incidence Greater than Placebo, Regardless of Causality Body System/Organ Class
Adverse Reaction Placebo
(%)
n=60 Ezetimibe
10 mg
(%)
n=65 Atorvastatin†
(%)
n=248 LIPTRUZET†
(%)
n=255
* Placebo-controlled combination study in which the active ingredients equivalent to LIPTRUZET were coadministered. † All doses.
Nervous system disorders
Dizziness 0 6 <1 2
Respiratory, thoracic, and mediastinal disorders
Coughing 0 3 <1 2
Gastrointestinal disorders
Abdominal pain 2 2 4 3
Nausea 0 2 5 3
Musculoskeletal and connective tissue disorders
Arthralgia 0 5 6 3
Muscle weakness 0 2 0 2
Musculoskeletal pain 3 8 5 4
Metabolism and nutrition disorders
Hyperkalemia 0 0 <1 2
Infections and infestations
Bronchitis 0 2 2 2
Sinusitis 0 3 2 2
Vascular disorders
Hot flushes 0 0 <1 2
Investigations
ALT increased 0 0 2 5
AST increased 0 0 <1 4
After completing the 12-week study, eligible patients were assigned to coadministered ezetimibe and atorvastatin equivalent to LIPTRUZET (10/10-10/80) or atorvastatin (10-80 mg/day) for an additional 48 weeks. The long-term coad |
