Vascepa

VASCEPA^® (icosapent ethyl) is indicated:

• as an adjunct to maximally tolerated statin therapy to reduce the risk of myocardial infarction, stroke, coronary revascularization, and unstable angina requiring hospitalization in adult patients with elevated triglyceride (TG) levels (≥ 150 mg/dL) and
  
  • established cardiovascular disease or
  • diabetes mellitus and 2 or more additional risk factors for cardiovascular disease.
• as an adjunct to diet to reduce TG levels in adult patients with severe (≥ 500 mg/dL) hypertriglyceridemia.

The effect of VASCEPA on the risk for pancreatitis in patients with severe hypertriglyceridemia has not been determined.

• Assess lipid levels before initiating therapy. Identify other causes of high triglyceride levels and manage as appropriate. (
  2.1 Prior to Initiation of VASCEPA

  • Assess lipid levels before initiating therapy. Identify other causes (e.g., diabetes mellitus, hypothyroidism, or medications) of high triglyceride levels and manage as appropriate.
  • Patients should engage in appropriate nutritional intake and physical activity before receiving VASCEPA, which should continue during treatment with VASCEPA.
  )
• Patients should engage in appropriate nutritional intake and physical activity before receiving VASCEPA, which should continue during treatment. (
  2.1 Prior to Initiation of VASCEPA

  • Assess lipid levels before initiating therapy. Identify other causes (e.g., diabetes mellitus, hypothyroidism, or medications) of high triglyceride levels and manage as appropriate.
  • Patients should engage in appropriate nutritional intake and physical activity before receiving VASCEPA, which should continue during treatment with VASCEPA.
  )
• The daily dose of VASCEPA is 4 grams per day taken as either
  
  • four 0.5 gram capsules twice daily with food or
  • two 1 gram capsules twice daily with food. (
    2.2 Dosage and Administration

    • The daily dose of VASCEPA is 4 grams per day taken as either:
      • four 0.5 gram capsules twice daily with food; or as
      • two 1 gram capsules twice daily with food.
    • Advise patients to swallow VASCEPA capsules whole. Do not break open, crush, dissolve, or chew VASCEPA.
    )
• Advise patients to swallow capsules whole. Do not break open, crush, dissolve, or chew VASCEPA. (
  2.2 Dosage and Administration

  • The daily dose of VASCEPA is 4 grams per day taken as either:
    • four 0.5 gram capsules twice daily with food; or as
    • two 1 gram capsules twice daily with food.
  • Advise patients to swallow VASCEPA capsules whole. Do not break open, crush, dissolve, or chew VASCEPA.
  )

VASCEPA capsules are supplied as:

• 0.5 gram amber-colored, oval, soft-gelatin capsules imprinted with V500
• 1 gram amber-colored, oblong, soft-gelatin capsules imprinted with VASCEPA

The available data from published case reports and the pharmacovigilance database on the use of VASCEPA in pregnant women are insufficient to identify a drug-associated risk for major birth defects, miscarriage or adverse maternal or fetal outcomes. In animal reproduction studies in pregnant rats, non-dose-related imbalances for some minor developmental findings were observed with oral administration of icosapent ethyl during organogenesis at exposures that were equivalent to the clinical exposure at the human dose of 4 g/day, based on body surface area comparisons. In a study in pregnant rabbits orally administered icosapent ethyl during organogenesis, there were no clinically relevant adverse developmental effects at exposures that were 5 times the clinical exposure, based on body surface area comparisons (

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

In pregnant rats given oral gavage doses of 0.3, 1 and 2 g/kg/day icosapent ethyl from gestation through organogenesis all drug treated groups had non-dose-related imbalances in visceral and skeletal findings, including 13^th reduced ribs, additional liver lobes, testes medially displaced and/or not descended, at human systemic exposures following a maximum oral dose of 4 g/day based on body surface comparisons.

In a multigenerational developmental study in pregnant rats given doses of 0.3, 1, 3 g/kg/day icosapent ethyl by oral gavage from gestation day 7-17, icosapent ethyl did not affect viability in fetuses (F₁ or F₂). Non-dose-related imbalances in findings of absent optic nerves and unilateral testes atrophy at human exposures based on the maximum dose of 4 g/day and on body surface area comparisons. Additional variations consisting of early incisor eruption and increased percent cervical ribs were observed at the same exposures. Pups from high dose treated dams exhibited decreased copulation rates, delayed estrus, decreased implantations and decreased surviving fetuses (F2) suggesting potential multigenerational effects of icosapent ethyl at 7 times human systemic exposure following 4 g/day dose based on body surface area comparisons across species.

In pregnant rabbits given oral gavage doses of 0.1, 0.3, and 1 g/kg/day icosapent ethyl from gestation through organogenesis, a decrease in body weight and food consumption was observed at the high dose of 1 g/kg/day (5 times the human exposure at the maximum dose of 4 g/day, based on body surface area comparisons). Slight increases in resorbed and dead fetuses were noted in the 1 g/kg/day group, but these were not significantly different from the control group. There were no differences between the icosapent ethyl groups and control group as to the number of

In pregnant rats given icosapent ethyl from gestation day 17 through lactation day 20 at 0.3, 1, 3 g/kg/day no adverse maternal or developmental effects were observed. However, complete litter loss (not dose-related) was noted in 2/23 litters at the low dose and 1/23 mid-dose dams by post-natal day 4 at human exposures at a maximum dose of 4 g/day, based on body surface area comparisons.