Epanova ® - Omega-3- carboxylic acids Manufacturer: AstraZeneca FDA Approval Date: 05/2014.
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Transcript of Epanova ® - Omega-3- carboxylic acids Manufacturer: AstraZeneca FDA Approval Date: 05/2014.
Epanova® - Omega-3-carboxylic acids
Manufacturer:
AstraZeneca
FDA Approval Date: 05/2014
Epanova® - Omega-3-carboxylic acids
Clinical Application
• Indications:• Treatment of severe hypertriglyceridemia
(≥ 500 mg/dL) as an adjunct to diet
• Place in therapy:• Used after diet changes have failed to
lower TG levels adequately
Epanova® - Omega-3-carboxylic acids
Clinical Application
• Contraindications:• Known hypersensitivity to Epanova or
any of its components
Epanova® - Omega-3-carboxylic acids
Clinical Application
• Warnings and Precautions:• LDL-C should be monitored during
treatment with Epanova as LDL has increased in some patients
• ALT/AST should be monitored periodically in patients with hepatic impairment
• Epanova should be used with caution in patients who have fish allergies
Epanova® - Omega-3-carboxylic acids
Clinical Application
• Pregnancy:• C
• Lactation:• Studies with fish oil have shown that
excretion into breast milk occurs at higher concentration than that in plasma and the effect of Epanova on infants is not known
Epanova® - Omega-3-carboxylic acids
Drug Facts
• Pharmacology:• The mechanism of action is not
completely understood. Potential mechanisms of action include:
• Acyl-CoA:1,2-diacylglycerol acetyltransferase inhibition
• Increased mitochondrial and peroxismal β-oxidation in the liver
Epanova® - Omega-3-carboxylic acids
Drug Facts
• Pharmacology:• The mechanism of action is not completely
understood. Potential mechanisms of action include:
• Decreased lipogenesis in the liver• Increased plasma lipoprotein lipase
activity• EPA and DHA are poor substrates for the
enzyme responsible for triglyceride synthesis
Epanova® - Omega-3-carboxylic acids
Drug Facts
• Pharmacokinetics:
ADirectly absorbed in the small intestine. Cmax 5-9 hours. Steady state concentrations of EPA and DHA are achieved after 2 weeks of repeat daily dosing.
DThe majority of EPA and DHA is incorporated in phospholipids, triglycerides and cholesteryl esters. Free unesterified fatty acids represent 0.8% of the EPA and 1.1% of the DHA.
MEPA and DHA are mainly oxidized in the liver.
EEpanova does not undergo renal excretion. EPA half-life is 37 hours, DHA half-life is 46.
Epanova® - Omega-3-carboxylic acids
Drug Interactions
• Drug Interactions – Object Drugs: • None
Epanova® - Omega-3-carboxylic acids
Drug Interactions
• Drug Interactions – Precipitant Drugs: • None
Epanova® - Omega-3-carboxylic acids
Drug Interactions
• Drug Interactions – Pharmacodynamic interactions: • Anticoagulants – may increase bleeding
time
Epanova® - Omega-3-carboxylic acids
Adverse Effects
• Common Adverse Effects:
Placebo Epanova 2g Epanova 4g
Diarrhea 2% 7% 15%
Nausea 1% 4% 6%
Abdominal pain or
discomfort
2% 3% 5%
Eructation <1% 3% 3%
Epanova® - Omega-3-carboxylic acids
Monitoring Parameters
• Efficacy Monitoring:• Monitor triglycerides
• Toxicity Monitoring:• Monitor for changes in INR as studies
with fish oil have shown an increased bleeding time
Epanova® - Omega-3-carboxylic acids
Prescription Information
• Dosing: 2 or 4 g once daily• Dosing is individualized according to
response and tolerability.
• Cost: – Epanova has not reached the market yet and a price has not been set by AstraZeneca
Epanova® - Omega-3-carboxylic acids
Literature Review
• Purpose: To evaluate the efficacy and safety of Epanova (OM3-FFA)…in subjects with severe hypertriglyceridemia (TGs ≥ 500 but < 2000)
• Design: Double-blind, randomized, parallel, 4-arm study
Kastelein, J., et al. Journal of Clinical Lipidology. 2014(8)94-106.
Epanova® - Omega-3-carboxylic acids
Literature Review
Kastelein, J., et al. Journal of Clinical Lipidology. 2014(8)94-106.
Inclusion criteria Exclusion criteria
≥ 18 years old Known lipoprotein lipase impairment
Not pregnant or lactating Hx of pancreatitis, symptomatic gallstone disease
BMI ≥ 20 Uncontrolled diabetes (A1c ≥ 9%)
Be willing to: maintain customary activity level, follow TLC diet, restrict
consumption of fish
Cancer in the past 2 years
Untreated or on already-established dosing of other lipid-lowering drugs
Cardiovascular event in the past 6 months
Poorly controlled HTN (≥160/≥100)
Abnormal ALT/AST, GFR, BG, platelets or Hgb
Epanova® - Omega-3-carboxylic acids
Literature Review
• Baseline characteristics:
Kastelein, J., et al. Journal of Clinical Lipidology. 2014(8)94-106.
Placebo (OO) Epanova 2 g Epanova 3 g Epanova 4 g
Number 99 100 101 99
Men 77 (78%) 80 (80%) 79 (78%) 71 (72%)
Mean age 51 ± 11 51 ± 10 51 ± 9 53 ± 11
White race 95 (96%) 93 (93%) 92 (91%) 88 (89%)
Diabetes 30 (30%) 39 (39%) 45 (45%) 36 (36%)
HTN 64 (65%) 69 (69%) 69 (68%) 67 (68%)
Statin/CAI users
34 (34%) 35 (35%) 35 (35%) 34 (34%)
Epanova® - Omega-3-carboxylic acids
Literature Review
• Treatment arms:• Olive oil (OO) 4 g/day x 12 weeks
• Epanova 2 g/day + OO 2 g/day x 12 weeks
• Epanova 3 g/day + OO 1 g/day x 12 weeks
• Epanova 4 g/day x 12 weeks
• Efficacy monitoring: Lipid panel
Kastelein, J., et al. Journal of Clinical Lipidology. 2014(8)94-106.
Epanova® - Omega-3-carboxylic acids
Literature Review
• Statistical analysis:• 332 patients needed for 80% power to
detect at least 20% difference in TG levels
• Intention-to-treat analysis, included participants with 1+ doses and 1+ efficacy assessments
Kastelein, J., et al. Journal of Clinical Lipidology. 2014(8)94-106.
Epanova® - Omega-3-carboxylic acids
Literature Review
• Primary endpoint: TG percentage change
• Secondary endpoint: non-HDL-C and HDL-C percentage change
Kastelein, J., et al. Journal of Clinical Lipidology. 2014(8)94-106.
Epanova® - Omega-3-carboxylic acids
Literature Review
• Results: (% Δ from baseline, 95% CI)
Significantly different from placebo: † p<0.05, ‡ p<0.01, * p<0.001
Kastelein, J., et al. Journal of Clinical Lipidology. 2014(8)94-106.
Placebo (OO) Epanova 2 g Epanova 3 g Epanova 4 g
TG -4.3% (-13.1 to 5.4)
-25.9% (-32.8 to -18.3)‡
-25.5% (-32.4 to -17.8)‡
-30.9% (-37.3 to -23.7)*
Non-HDL-C
2.5% (-2.3 to 7.6)
-7.6% (-12.0 to -3.0)†
-6.9% (-11.4 to -2.2)†
-9.6% (-14.0 to -5.1)‡
HDL-C 1.9% (-2.0 to 6.0)
7.4% (3.2 to 11.7)
3.8% (-0.3 to 8.0)
5.8% (1.7 to 10.1)
Total-C 3.2% (-1.0 to 7.5)
-5.4% (-9.3 to -1.4)†
-4.9% (-8.7 to -0.8)
-7.5% (-11.2 to -3.5)‡
LDL-C 3.0% (-2.9 to 9.3)
19.2% (12.3 to 26.6)‡
14.3% (7.6 to 21.4)
19.4% (12.4 to 26.8)*
Epanova® - Omega-3-carboxylic acids
Literature Review
• Adverse events:
Kastelein, J., et al. Journal of Clinical Lipidology. 2014(8)94-106.
Placebo (OO) Epanova 2 g Epanova 3 g Epanova 4 g
Diarrhea 2.0% 10.0% 5.9% 10.1%
Nausea 1.0% 6.0% 8.9% 5.1%
Abdominal pain/discomfort
1.0% 4.0% 1.0% 1.0%
Eructation 1.0% 3.0% 4.0% 4.0%
Infections (all) 11.1% 14.0% 6.9% 12.1%
Epanova® - Omega-3-carboxylic acids
Literature Review
• Discussion:• Total N = 364
• No significant difference between treatment groups for those who discontinued
• Discontinuation due to GI upset was 5-7% for Epanova and 0% for placebo
Kastelein, J., et al. Journal of Clinical Lipidology. 2014(8)94-106.
Epanova® - Omega-3-carboxylic acids
Literature Review
• Discussion:• Epanova reduced TG levels by at least
25%
• The degree of TG lowering was less with 3 g/day than the 2 or 4 g/day
• Non-HDL-C was also significantly lowered in each Epanova group
• LDL was significantly increased in Epanova groups
Kastelein, J., et al. Journal of Clinical Lipidology. 2014(8)94-106.
Epanova® - Omega-3-carboxylic acids
Summary
• Epanova is indicated for the treatment of severe hypertriglyceridemia (≥ 500 mg/dL) as an adjunct to diet.
• Epanova should be used after diet changes have failed to lower triglycerides.
• Epanova® has no pharmacokinetic interactions but a pharmacodynamic interaction occurs between Epanova® and anticoagulants - increased bleeding time
• Epanova is commonly dosed between 2 and 4 grams daily but dosing is individualized
Epanova® - Omega-3-carboxylic acids
References
1. http://www.epanovahcp.com. 06/14.
2. Epanova package insert. AstraZeneca. May 2014.
3. Kastelein, J.J.P., Maki, K.C., et al. Omega-3 free fatty acids for the treatment of severe hypertriglyceridemia: The EpanoVa fOr Lowering Very high triglyceridEs (EVOLVE) trial. Journal of Clinical Lipidology (2014)8;94-106.