VASCEPA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VASCEPA (VASCEPA).
Icosapent ethyl is a prodrug that is de-esterified to the active metabolite, eicosapentaenoic acid (EPA). EPA reduces hepatic very low-density lipoprotein (VLDL) triglyceride synthesis and secretion, and increases triglyceride clearance from circulating VLDL particles.
| Metabolism | Icosapent ethyl is hydrolyzed by intestinal lipases to EPA, which is then further metabolized primarily via beta-oxidation. Minor metabolism by CYP450 enzymes (CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4) and conjugation. |
| Excretion | Primarily hepatic metabolism; <1% excreted unchanged in urine. Fecal excretion accounts for <5%. |
| Half-life | Terminal elimination half-life: ~89 hours (range 66-120 hours) for icosapent ethyl; steady-state achieved after 4 weeks. |
| Protein binding | >99% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Vd/F: 88 L (approx. 1.1 L/kg); indicates distribution primarily in plasma and extracellular fluid. |
| Bioavailability | Oral bioavailability: ~20-30% (as icosapent ethyl) under fed conditions; absorption enhanced with high-fat meals. |
| Onset of Action | Serum triglyceride reduction observed within 2-4 weeks of oral dosing; maximal effect by 6-8 weeks. |
| Duration of Action | Duration of triglyceride-lowering effect persists for up to 2 weeks after discontinuation; clinical effect maintained with continued therapy. |
4 grams orally once daily (two 0.5-gram capsules twice daily or one 1-gram capsule twice daily) with or without food.
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Not studied in severe renal impairment (eGFR <30 mL/min/1.73 m²); use with caution. |
| Liver impairment | No specific dose adjustment per Child-Pugh classification. Not studied in patients with hepatic impairment; use with caution. |
| Pediatric use | Safety and efficacy not established in pediatric patients; no recommended dose. |
| Geriatric use | No specific dose adjustment required. Elderly patients may have age-related renal impairment; monitor renal function as per standard practice. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for VASCEPA (VASCEPA).
| Breastfeeding | It is not known whether icosapent ethyl or its metabolites are excreted in human milk. M/P ratio not available. Caution should be exercised when administered to a nursing woman. Consider the developmental and health benefits of breastfeeding along with the mother's clinical need for VASCEPA and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition. |
| Teratogenic Risk | VASCEPA (icosapent ethyl) is classified as FDA Pregnancy Category C. No adequate and well-controlled studies in pregnant women. In animal studies, no evidence of fetal harm at doses up to 4 times the human systemic exposure. However, because animal reproduction studies are not always predictive of human response, use during pregnancy only if clearly needed. First trimester: No known specific risk. Second and third trimesters: No known adverse effects, but no human data available. |
■ FDA Black Box Warning
None.
| Serious Effects |
["History of hypersensitivity to icosapent ethyl or any component of the formulation"]
| Precautions | ["Increased risk of atrial fibrillation or atrial flutter, particularly in patients with prior cardiac arrhythmias or cardiovascular risk factors","Increased risk of bleeding in patients taking anticoagulants or antiplatelet agents; monitor for signs of bleeding","Potential hypersensitivity reactions including anaphylaxis and angioedema","Elevated liver function tests; monitor periodically","May cause diarrhea, nausea, abdominal pain","Contains ethyl esters; avoid in patients with known hypersensitivity to fish or shellfish"] |
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| Fetal Monitoring | No specific maternal-fetal monitoring required beyond routine prenatal care. Monitor pregnant women for any adverse effects related to the drug, such as bleeding events or arrhythmias, although these are not specifically required. No fetal monitoring indicated. |
| Fertility Effects | No adequate data on the effect of VASCEPA on human fertility. Animal studies did not show impairment of fertility at doses up to 4 times the human systemic exposure. |