ministration of ezetimibe plus atorvastatin had an overall safety profile similar to that of atorvastatin alone.
Ezetimibe
In 10 double-blind, placebo-controlled clinical trials, 2396 patients with primary hyperlipidemia (age range 9-86 years, 50% women, 90% Caucasians, 5% Blacks, 3% Hispanics, 2% Asians) and elevated LDL-C were treated with ezetimibe 10 mg/day for a median treatment duration of 12 weeks (range 0 to 39 weeks).
Adverse reactions reported in ≥2% of patients treated with ezetimibe and at an incidence greater than placebo regardless of causality assessment are shown in Table 3.
Table 3: Clinical Adverse Reactions Occurring in ≥2% of Patients Treated with Ezetimibe and at an Incidence Greater than Placebo, Regardless of Causality Body System/Organ Class
Adverse Reaction Ezetimibe 10 mg (%)
n=2396 Placebo (%)
n=1159
Gastrointestinal disorders
Diarrhea 4.1 3.7
General disorders and administration site conditions
Fatigue 2.4 1.5
Infections and infestations
Influenza 2.0 1.5
Sinusitis 2.8 2.2
Upper respiratory tract infection 4.3 2.5
Musculoskeletal and connective tissue disorders
Arthralgia 3.0 2.2
Pain in extremity 2.7 2.5
Atorvastatin
In an atorvastatin placebo-controlled clinical trial database of 16,066 patients (8755 atorvastatin vs. 7311 placebo; age range 10–93 years, 39% women, 91% Caucasians, 3% Blacks, 2% Asians, 4% other) with a median treatment duration of 53 weeks, 9.7% of patients on atorvastatin and 9.5% of the patients on placebo discontinued due to adverse reactions regardless of causality.
The most commonly reported adverse reactions (incidence ≥2% and greater than placebo) regardless of causality, in patients treated with atorvastatin in placebo controlled trials (n=8755) were: nasopharyngitis (8.3%), arthralgia (6.9%), diarrhea (6.8%), pain in extremity (6.0%), and urinary tract infection (5.7%).
Table 4 summarizes the frequency of clinical adverse reactions, regardless of causality, reported in ≥2% and at a rate greater than placebo in patients treated with atorvastatin (n=8755), from seventeen placebo-controlled trials.
Table 4: Clinical Adverse Reactions Occurring in > 2% in Patents Treated with any dose of Atorvastatin and at an Incidence Greater than Placebo Regardless of Causality (% of patients). Adverse Reaction* Any dose
n=8755 Atorvastatin
10 mg
n=3908 Atorvastatin
20 mg
n=188 Atorvastatin
40 mg
n=604 Atorvastatin
80 mg
n=4055 Placebo
n=7311
* Adverse Reaction >2% in any dose greater than placebo
Nasopharyngitis 8.3 12.9 5.3 7.0 4.2 8.2
Arthralgia 6.9 8.9 11.7 10.6 4.3 6.5
Diarrhea 6.8 7.3 6.4 14.1 5.2 6.3
Pain in extremity 6.0 8.5 3.7 9.3 3.1 5.9
Urinary tract infection 5.7 6.9 6.4 8.0 4.1 5.6
Dyspepsia 4.7 5.9 3.2 6.0 3.3 4.3
Nausea 4.0 3.7 3.7 7.1 3.8 3.5
Musculoskeletal pain 3.8 5.2 3.2 5.1 2.3 3.6
Muscle spasms 3.6 4.6 4.8 5.1 2.4 3.0
Myalgia 3.5 3.6 5.9 8.4 2.7 3.1
Insomnia 3.0 2.8 1.1 5.3 2.8 2.9
Pharyngolaryngeal pain 2.3 3.9 1.6 2.8 0.7 2.1
6.2 Postmarketing ExperienceBecause the reactions below are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
The additional events described below have been identified during post-approval use of ezeti |
