PHARMACOLOGY UPDATE
Omega-3-Carboxylic Acid Capsules (Epanova®)
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; and Assistant Professor of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA
Drs. Elliott and Chan report no financial relationships relevant to this field of study.
The FDA has approved the first free fatty acid form of omega-3. Previous formulations have been ethyl esters of omega-3-acids. The omega-3-carboxylic acid is a fish oil-derived mixture of 50-60% eicosapentaenoic acid (EPA) and 15-25% docosahexaenoic acid (DHA) along with other potentially active omega-3 fatty acids. It is marketed by AstraZeneca as Epanova.
Indications
Omega-3-carboxylic acid is indicated as an adjunct to diet to reduce triglyceride (TG) levels in adults with severe hypertriglyceridemia (≥ 500 mg/dL).1
Dosage
The recommended dose is 2 grams or 4 grams once daily based on response and tolerability.1 It may be taken without regard to meals. Omega-3-carboxylic acid is available as 1 gram capsules. Each capsule contains at least 850 mg of polyunsaturated fatty acids, including multiple omega-3 fatty acids.
Potential Advantages
Omega-3-carboxylic acid (Epanova) provides an alternative to the two marketed omega-3-acid ethyl esters (Lovaza® and Vascepa®).
Potential Disadvantages
In some patients, omega-3-carboxylic acid may increase LDL-C levels.1 Adverse events reported with omega-3-carboxylic acid include diarrhea (7-15%), nausea (4-6%), and abdominal pain or discomfort (3-5%) compared to 1-2% for placebo (olive oil).1 Omega-3-fatty acids may increase bleeding time.1
Comment
Omega-3-carboxylic acid was evaluated in a randomized, double-blind, placebo-controlled, parallel-group, 12-week study.1 Subjects with TG levels between 500 and 2000 mg/dL (median 694 mg/dL) were randomized to omega-3-carboxylic acid, 2, 3, or 4 grams per day or olive oil placebo. Other median lipid levels at baseline were: non-HDL-C 217 mg/dL, LDL-C 81 mg/dL, and HDL-C 28 mg/dL. Statins and ezetimibe were permitted during the study. Thirty-five percent were on a statin and/or ezetimibe. The treatment differences for TG between placebo and omega-3-carboxylic acid were -16% and -21% for the 2 g dose and 4 g dose, respectively. For non-HDL-C, reductions were 7% and 10%, respectively. These reductions were statistically significant. LDL-C was increased by 13% and 15%. Statistical significance tests were not performed for LDL-C.1 The effect of the 3 g dose was not meaningfully different than the 2 g dose.1 Omega-3 fatty acids have not been shown to affect the risk of pancreatitis or cardiovascular mortality or morbidity.1
Clinical Implications
Epanova is the fatty acid form of EPA and DHA along with other fatty acids. The previously marketed products are ethyl esters. Since esterified products are de-esterified during absorption, it is not certain if the new fatty acid form offers any clinical advantage. Similar to Lovaza, which contains EPA and DHA, Epanova increased LDL-C while icosapent ethyl, which contains only EPA, showed no significant change.2 AstraZeneca plans to evaluate the safety and efficacy on cardiovascular outcomes in combination with a statin in subjects with hypertriglyceridemia and high cardiovascular risk at a dose of 4 gm per day (estimated completion date 2019).3 A similar study with icosapent ethyl (4 g) is expected to be completed in 2016.4 Generally, omega-3 fatty acid supplementation has not been shown to reduce cardiovascular mortality and morbidity, cancer incidence, non-vascular death, or total mortality.5,6 The wholesale cost for Epanova was not available at the time of this review.
REFERENCES
- Epanova Prescribing Information. Wilmington, DE: AstraZeneca Pharmaceuticals; May 2014.
- Bays HE, et al. Am J Cardiol 2011;108:682-690.
- https://clinicaltrials.gov/ct2/show/NCT02104817?term=epanova&rank=5. Accessed June 19, 2014.
- https://clinicaltrials.gov/ct2/show/NCT02104817?term=epanova&rank=5. Accessed June 19, 2014.
- Roncaglioni MC, et al. N Engl J Med 2013;368:1800-1808.
- Zhang YF, et al. BMC Public Health 2014;14:204-216.
