The FDA has approved Vascepa/Lovaza fish oil, which contains Omega 3 acid ethyl esters, for lowering the risk of cardiovascular illnesses. It lessens the development of plaque and cardiovascular mortality (EVAPORATE Trial).

Vascepa/ Lovaza Uses:

• Dietary supplement:

  • Utilised as dietary supplements for people at early risk of coronary artery disease

Note:

• The American Heart Association (AHA) recommends that people who have never had coronary heart disease (CHD) eat a variety of fish, especially oily fish (like  salmon), at least twice a week, or every day in the case of people who have.

• Hypertriglyceridemia (Lovaza and Vascepa):

  • In adults with severe hypertriglyceridemia, as a supplement to the diet, to lower triglyceride levels.

• Off Label Use of Omega-3-acid ethyl esters Adults:

  • Cardiovascular risk reduction with mild hypertriglyceridemia
  • IgA nephropathy

Note:

• The Endocrine Society advises using omega-3 fatty acids alone or in combination with HMG-CoA reductase inhibitors for triglyceride levels above 1,000 mg/dL.
• Many OTC products with omega-3 fatty acids are promoted as nutritional supplements, however they lack FDA-approved purposes and might not have the same concentrations of the active ingredient.

Vascepa/ Lovaza (Omega-3-acid ethyl esters) Dose in Adults

Omega-3-acid ethyl esters dosage for the off-label therapy of mild hypertriglyceridemia and cardiovascular risk reduction:

Note:

• This treatment may be beneficial for patients who have a history of cardiovascular disease (CVD), diabetes, and other CVD risk factors, are on a stable dose of  statins, have LDL cholesterol below 100 mg/dL, but still have fasting triglycerides between 150 and 499 mg/dL.

Oral:

• Vascepa: 2 grams twice per with meals.

Vascepa/ Lovaza Dose in the treatment of Hypertriglyceridemia:

• Lovaza:

  • Either 2 g (2 capsules) twice a day or 4 g (4 capsules) orally once daily.

• Vascepa:

  • 2 g should be taken orally twice daily with meals—either two 1 g capsules or four 0.5 g capsules.

Lovaza Dose in the treatment of IgA nephropathy (off-label):

Oral:

• 4 g (4 capsules) of lovaza once day.

Omega-3-acid ethyl esters Use in children:

Children's use of Omega-3-acid ethyl esters has not been proven to be safe or effective.

Pregnancy Risk Factor C

• Animal reproduction studies have shown that adverse events can be observed.
• It is important to get enough omega-3 fatty acids during pregnancy.
• Maternal supplementation or diet may have an impact on foetal quantities of omega-3 fatty acids, such as eicosapentaenoic and docosahexaenoic acids (DHA).
• As normal fetal development requires, glyceride levels increase in pregnancy.
• Supplements containing omega-3 fatty acids may be used in supervised dietary programmes if increases are more than anticipated.
• For women with extremely severe hypertriglyceridemia or who are at a high risk of developing pancreatitis, prescription omega-3 fatty acid supplements may be an alternative.

Omega-3-acid ethyl esters use during breastfeeding:

• Breast milk contains Omega-3 fatty acids and dietary supplements can affect milk concentrations.
• According to the manufacturer of the product, when deciding whether to continue or stop breastfeeding during therapy, it should consider the risks to infant exposure, the benefits to the infant and the benefits to the mother.

Omega-3-acid ethyl esters Dose in Kidney Disease:

• No dosage adjustments are provided in the manufacturer's labeling (has not been studied). EPA and DHA are not renally excreted.

Vascepa Dose in Liver Disease:

• No dosage adjustments are provided in the manufacturer's labeling (has not been studied).

Common Side Effects of Vascepa (Omega-3-acid ethyl esters):

• Gastrointestinal:

  • Diarrhea

Less Common Side Effects:

• Gastrointestinal:

  • Dysgeusia
  • Eructation
  • Dyspepsia
  • Nausea
  • Abdominal Pain

• Neuromuscular & Skeletal:

  • Arthralgia

Side effects of Omega-3-acid ethyl esters (Frequency not known):

• Hematologic & Oncologic:

  • Prolonged Bleeding Time

• Central Nervous System:

  • Fatigue

• Endocrine & Metabolic:

• • Increased LDL Cholesterol

• Respiratory:

  • Nasopharyngitis
  • Oropharyngeal Pain

• Gastrointestinal:

  • Constipation
  • Flatulence
  • Abdominal Distension
  • Gastrointestinal Disease
  • Vomiting

• Dermatologic:

  • Pruritus
  • Skin Rash
•  

• Hepatic:

  • Increased Serum Alanine Aminotransferase
  • Increased Serum Aspartate Aminotransferase

Contraindications to Vascepa (Omega-3-acid ethyl esters):

• hypersensitivity to any ingredient in the mix, including omega-3 fatty acids (eg, anaphylactic response)

Warnings and precautions

• Fish allergy

  • Patients with an allergy to shellfish or fish should be cautious.

• The Lipid Effects

  • Monitor LDL levels periodically.
  • May raise LDL levels

• Longer bleeding time

  • Some clinical studies using omega-3 fatty oils have shown that bleeding times do not increase beyond normal limits.
  • Patients with coagulopathy and those on anticoagulation therapy or therapeutic anticoagulation should be cautious.
  • When starting or changing the dosage of omega-3 fatty acids in patients taking warfarin, watch for changes in INR.

• Hepatic effects

  • Monitor the hepatic transaminases of patients with hepatic impairment periodically.
  • The ALT could increase without AST concurrently

• Atrial fibrillation (AF):

  • Recurrent AF may occur in patients with chronic or symptomatic AF.
  • Omega-3 fatty acids cannot be utilised to treat the disorder known as flutter or AF.
  • In clinical investigations, omega-3 fatty acid therapy was used more frequently than a placebo.
  • There is little clinical importance for these data.

• Conditions that are associated with abnormal lipids

  • To avoid lipid abnormalities, concurrent diseases like diabetes, hypothyroidism, or excessive alcohol use can be treated.

Omega-3-acid ethyl esters (fish oil): Drug Interaction

Monitoring Parameters:

• Triglycerides and other lipids (LDL-C) need to be kept under regular and baseline observation.
• Regularly check the levels of hepatic transaminases, especially ALT, in individuals with hepatic impairment.

2013 ACC/AHA Blood Cholesterol Guideline recommendations (Stone, 2013):

• Examine your GI system, your skin, and your bleeding during treatment.

How to administer Vascepa (Omega-3-acid ethyl esters)?

Lovaza:

• Give the medication whole; don't break, crush, dissolve, or chew it. 

• Both with and without food, administer.

Vascepa:

• Take with meals

• Give the medication whole; don't break, crush, dissolve, or chew it. 

Mechanism of action of Vascepa (Omega-3-acid ethyl esters):

• Reduced triglyceride-rich very-low-density lipoprotein synthesis by the liver.
• Some proposed mechanisms include inhibition of acyl CoA1:2, diacylglycerol-acyltransferase, increased liver mitochondrial and peroxisomal benzo-oxidation, as well as a decrease in hepatic triglyceride production.

Absorption:

• Direct absorption of Omega-3 carboxylic acid occurs in the small intestine.
• For baseline-adjusted DHA, a 40% rise in AUC was seen.
• Comparing high-fat meal administration to fasting settings, an increase in overall exposure to total and free baseline-adjusted EPA is seen.

Icosapent ethyl:

• EPA,

Protein binding:

• EPA:  over 99%

Metabolism:

• EPA: minor via CYP-450

• The small intestine absorbs a de-esterified active metabolite. Comparable to fatty acids obtained from dietary sources, EPA and DHA  are primarily oxidised in the liver.

Half-life elimination:

• DHA: ~46 hours
• EPA: ~37 to 89 hours;

Time to peak plasma concentrations:

Omega-3-carboxylic acids:

• Following repeat dosing with low-fat meals for ~2 weeks (steady-state)
• EPA: 5 to 8 hours
• DHA: 5 to 9 hours

Icosapent ethyl:

• EPA: ~5 hours

International Brands of Omega-3-acid ethyl esters:

• Dialyvite Omega-3 Concentrate
• Expecta LIPIL
• Fish Oil Concentrate
• Lovaza
• Maximum Red Krill
• Ocean Blue MiniCaps Omega-3
• Odorless Coated Fish Oil
• Omega Power
• Omega-3 2100
• Omega-3 Fish Oil Ex St
• Omega-3 IQ
• Pro Nutrients Omega 3
• Salmon Oil-1000
• Sam-E.P.A.
• Sea-Omega
• Triklo
• Vascepa
• Agemo
• Dualtis
• Epax
• Equiplen
• Nebbaro
• Omacor
• Omaron
• Ysomega

Omega-3-acid ethyl esters Brand Names in Pakistan:

No Brands Available in Pakistan.