Lovaza

Omega-3 Dyslipidemic Agents

Lovaza:
Take with or without food. In clinical trials, Lovaza capsules were administered with meals.
Capsules should be swallowed whole. Advise patients not to break open, crush, dissolve or chew.
Omtryg:
Take with meals.
Capsules should be swallowed whole. Advise patients not to break open, crush, dissolve or chew.
Epanova:
Take with or without food. In clinical trials, Epanova capsules were administered without regard to meals.
Capsules should be swallowed whole. Advise patients not to break open, crush, dissolve or chew.

coagulopathy / Delayed / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
atrial flutter / Early / Incidence not known
atrial fibrillation / Early / Incidence not known

constipation / Delayed / Incidence not known
prolonged bleeding time / Delayed / Incidence not known
elevated hepatic enzymes / Delayed / Incidence not known
hypercholesterolemia / Delayed / Incidence not known

diarrhea / Early / 7.0-15.0
nausea / Early / 4.0-6.0
abdominal pain / Early / 3.0-5.0
dysgeusia / Early / 4.0-4.0
eructation / Early / 3.0-4.0
dyspepsia / Early / 3.0-3.0
rash / Early / 1.8-1.8
vomiting / Early / Incidence not known
ecchymosis / Delayed / Incidence not known
epistaxis / Delayed / Incidence not known
urticaria / Rapid / Incidence not known
pruritus / Rapid / Incidence not known
fatigue / Early / Incidence not known
pharyngitis / Delayed / Incidence not known
arthralgia / Delayed / Incidence not known

Lovaza, Omacor, Triklo

Rx

Mixtures of ethyl esters or free fatty acids derived from fish oil primarily composed of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)
Used as an adjunct to diet to reduce triglyceride levels in adult patients with severe (500 mg/dL or greater) hypertriglyceridemia
Unknown effect on the risk for pancreatitis or cardiovascular morbidity and mortality

2 or 4 g PO once daily. Individualize dosage according to response and tolerability.

4 g PO once daily or 2 g PO twice daily.

4.8 g PO once daily or 2.4 g PO twice daily.

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

There are no drug interactions associated with Fish Oil, Omega-3 Fatty Acids (FDA-approved) products.

Lovaza/Omacor/Omega-3-Acid Ethyl Esters/Omega-3-Acid Ethyl Esters, Eicosapentaenoic Acid (EPA), Docosahexaenoic Acid (DHA)/Triklo Oral Cap: 1g, 465-375mg

4 capsules/day PO.

4 capsules/day PO.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

The mechanism of action of fish oil, omega-3 fatty acids for the treatment of hypertriglyceridemia is not completely understood. Omega-3 fatty acids reduce the hepatic production of triglyceride (TG)-rich very-low-density lipoproteins and may increase the removal rate of TG-rich lipoproteins by increasing lipoprotein lipase activity. Inhibition of acyl-CoA:1,2-diacylglycerol acyltransferase, increased mitochondrial and hepatic peroxisomal beta-oxidation, decreased hepatic lipogenesis, and increased plasma lipoprotein lipase activity are potential mechanisms of action.

Fish oil, omega-3 fatty acids is administered orally. When administered as ethyl esters, omega-3 fatty acids induce significant, dose-dependent increases in serum phospholipid eicosapentaenoic acid (EPA) content. Increases in docosahexaenoic acid (DHA) content were less marked and not dose-dependent when administered as ethyl esters.[43902] [57074] Following repeat dosing of omega-3 carboxylic acids under low-fat meal conditions for approximately 2 weeks, maximum plasma concentrations are achieved 5 to 8 hours after dosing for total EPA and between 5 to 9 hours after dosing for total DHA. Steady-state concentrations of EPA and DHA in plasma are achieved within 2 weeks of repeat daily dosing with omega-3 carboxylic acids. EPA and DHA from omega-3 carboxylic acids are mainly oxidized in the liver similar to fatty acids derived from dietary sources.[57124]
 
Affected cytochrome P450 isoenzymes: none
While omega-3-fatty acid containing products have shown increased hepatic concentrations of CYP450 and activities of certain CYP450 isoenzymes in rats, the potential to induce CYP450 activities in humans has not been studied. However, the free forms of the EPA and DHA are typically undetectable in human circulation. Clinically significant interactions of fish oil, omega-3 fatty acids with other drugs due to inhibition or induction of CYP450 mediated metabolism are not expected.[43902] [57074] [57124]

Lovaza: Lovaza was administered with meals in clinical trials.
 
Omtryg: Administration of Omtryg under fasted condition in clinical trials resulted in decreases in the peak (Cmax) and total (AUC0-72h) exposure by up to 20 to 80-fold, respectively, for total plasma EPA and by up to 2 to 4-fold, respectively, for total plasma DHA, in comparison to those observed under fed condition (high-fat high-calorie meal).
 
Epanova: Epanova was administered without regard to meals in clinical trials. Administration of a single dose of Epanova with a high-fat meal increased the overall exposure of total and free baseline-adjusted EPA by approximately 140% and 80%, respectively, compared to fasting conditions. There was no change in overall exposure of baseline-adjusted total DHA; however, there was a 40% increase in AUC for baseline-adjusted free DHA. Overall exposures of unadjusted total and free EPA increased by 80% and 50%, respectively, although there was no change in overall exposure for unadjusted total and free DHA.

Use fish oil, omega-3 fatty acids during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is unknown whether fish oil, omega-3 fatty acids can cause fetal harm or affect reproductive capacity. A 20% reduction in live births and 40% reduction in pup survival to postnatal day 4 were observed following oral administration of fish oil, omega-3 fatty acid to pregnant rats at doses 7-times the maximum recommended human dose (MRHD).

Use fish oil, omega-3 fatty acids with caution in breast-feeding mothers. Studies demonstrate excretion in human milk; however, the effect of this excretion on the infant is unknown. An animal study in lactating rates demonstrated drug concentrations were 6- to 14-times higher in milk than in plasma.