man systemic exposure following an oral dose of 4 g/day based on a body surface area comparison).
In pregnant rabbits given oral gavage doses of 375, 750, and 1,500 mg/kg/day from gestation day 7 through 19, no findings were observed in the fetuses in groups given 375 mg/kg/day (2 times human systemic exposure following an oral dose of 4 g/day based on a body surface area comparison). However, at higher doses, evidence of maternal toxicity was observed (4 times human systemic exposure following an oral dose of 4 g/day based on a body surface area comparison).
Nursing Mothers
It is not known whether omega-3-acid ethyl esters are excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when LOVAZA is administered to a woman who is breastfeeding.
Pediatric Use
Safety and effectiveness in pediatric patients under 18 years of age have not been established.
Geriatric Use
A limited number of patients older than 65 years were enrolled in the clinical studies. Safety and efficacy findings in subjects older than 60 years did not appear to differ from those of subjects younger than 60 years.
ADVERSE REACTIONS
Treatment-emergent adverse events reported in at least 1% of patients treated with LOVAZA 4 g per day or placebo during 8 randomized, placebo-controlled, double-blind, parallel-group studies for HTG are listed in Table 3. Adverse events led to discontinuation of treatment in 3.5% of patients treated with LOVAZA and 2.6% of patients treated with placebo.
Table 3. Adverse Events in Randomized, Placebo-Controlled, Double-Blind, Parallel-Group Studies for Very High TG Levels (≥500 mg/dL) That Used LOVAZA 4 g per Day BODY SYSTEM
Adverse Event LOVAZA
(N = 226) Placebo*
(N = 228)
n % n %
Subjects with at least 1 adverse event 80 35.4 63 27.6
Body as a whole
Back pain 5 2.2 3 1.3
Flu syndrome 8 3.5 3 1.3
Infection 10 4.4 5 2.2
Pain 4 1.8 3 1.3
Cardiovascular
Angina pectoris 3 1.3 2 0.9
Digestive
Dyspepsia 7 3.1 6 2.6
Eructation 11 4.9 5 2.2
Skin
Rash 4 1.8 1 0.4
Special senses
Taste perversion 6 2.7 0 0.0
Adverse events were coded using COSTART, version 5.0. Subjects were counted only once for each body system and for each preferred term.
*Placebo was corn oil for all studies.
Additional adverse events reported by 1 or more patients from 22 clinical studies for HTG are listed below:
Body as a Whole
Enlarged abdomen, asthenia, body odor, chest pain, chills, suicide, fever, generalized edema, fungal infection, malaise, neck pain, neoplasm, rheumatoid arthritis, and sudden death.
Cardiovascular System
Arrhythmia, bypass surgery, cardiac arrest, hyperlipemia, hypertension, migraine, myocardial infarct, myocardial ischemia, occlusion, peripheral vascular disorder, syncope, and tachycardia.
Digestive System
Anorexia, constipation, dry mouth, dysphagia, colitis, fecal incontinence, gastritis, gastroenteritis, gastrointestinal disorder, increased appetite, intestinal obstruction, melena, pancreatitis, tenesmus, and vomiting.
Hematologic-Lymphatic System
Lymphadenopathy.
Infections and Infestations
Viral infection.
Metabolic and Nutritional Disorders
Edema, hyperglycemia, increased ALT, and increased AST.
Musculoskeletal System
Arthralgia, arthritis, myalgia |
