Vascepa
Vascepa
Generic Name
Vascepa
Mechanism
- EPA incorporation into cell membranes → decreases lipogenesis and increases fatty acid oxidation.
- Inhibition of hepatic VLDL‑TG production by reducing *diacylglycerol acyltransferase* activity.
- Reduced secretion of apolipoprotein B‑100 → lower LDL‑remnant particles.
- Anti‑inflammatory effect via modulation of eicosanoid pathways (reduced prostaglandin‑E₂, thromboxane A₂).
- Improvement in endothelial function and reduced platelet aggregation, contributing to cardiovascular protection (shown in the REDUCE‑IT trial).
Pharmacokinetics
| Parameter | Details |
| Absorption | Oral, best absorbed with food (≥15 % with high‑fat meal). Peak plasma EPA at ~3 h post‑dose. |
| Distribution | Widely distributed; lipophilic; ~30 % plasma protein binding (free fraction ∼70 %). |
| Metabolism | Esterase‑mediated hydrolysis → EPA; hepatic β‑oxidation. Minimal CYP450 involvement. |
| Elimination | Excreted mainly via bile and feces; renal excretion <5 %. |
| Half‑life | EPA plasma half‑life ~9–12 h; continuous dosing achieves steady state by ~3–4 weeks. |
| Drug Interactions | Low potential; may potentiate anticoagulation when combined with warfarin or DOACs (monitor INR/anti‑Xa). No significant CYP450 inhibition/induction. |
Indications
- Triglyceride lowering: fasting TG ≥ 200 mg/dL (≥ 150 mg/dL when ASCVD present) despite maximally tolerated statin therapy.
- Cardiovascular risk reduction: Patients with ASCVD or high‑risk metabolic syndrome; shown to reduce major adverse cardiovascular events (MACE) by 25 % in the REDUCE‑IT trial.
- Adjunct to statin therapy: Not a substitute but an add‑on for residual hypertriglyceridemia.
Contraindications
- Contraindications: Known hypersensitivity to icosapent ethyl, fish oil, or ethyl ester moieties.
- Warnings:
- Use with caution in patients on anticoagulants (increased bleeding risk).
- Mild elevation of hepatic transaminases; monitor in patients with pre‑existing liver disease.
- Not indicated for acute coronary syndrome; evidence supports chronic use.
Dosing
| Step | Dose | Schedule |
| Initiation | 2 g (1 g BID) | With meals |
| Maintenance | 4 g (2 g BID) | With meals; can be taken as single 4 g dose if tolerated (e.g., evening). |
| Titration | Increase to 4 g over 2 weeks if TG remain >200 mg/dL. | Follow plasma TG response after 6–8 weeks. |
• Swallow capsules whole; may cause fishy aftertaste or belching.
• Do not split doses other than the two‑tablet formulation; keep capsules intact.
Adverse Effects
- Common (≥ 2 %):
- Gastrointestinal: belching, nausea, indigestion, fishy taste, diarrhea.
- Headache, mild dizziness.
- Transient mild‑reversible rise in serum *ALT/AST* (< 3× ULN).
- Serious (≤ 0.05 %):
- Bleeding episodes (especially when combined with warfarin or antiplatelets).
- Myopathy symptoms rare, no reported rhabdomyolysis.
- Rare hypersensitivity reactions (rash, urticaria).
Monitoring
- Baseline: fasting lipid panel, liver function tests (ALT, AST, ALP, bilirubin), serum creatinine, and coagulation profile if on anticoagulants.
- Follow‑up:
- TG and LDL at 6–8 weeks, then every 3–6 months.
- LFTs at 6 weeks, then annually.
- INR/anti‑Xa if on warfarin or DOAC; adjust dose as needed.
- Screen for weight changes or signs of bleeding.
Clinical Pearls
- Red‑ucE‑IT triumph: The pivotal trial randomized > 8,000 patients; icosapent ethyl reduced major adverse cardiac events by 25 % vs placebo when added to statins.
- Dose matters: The 4 g daily dose is evidence‑based; lower doses provide minimal TG reduction (< 15 %).
- Safety with statins: Co‑administration is well tolerated; no significant interaction with statin metabolism.
- Fishy vs fish‑free: Unlike generic fish‑oil capsules, Vascepa contains pure EPA (no DHA) and is formulated to minimize fishy aftertaste.
- Patient adherence: Educate patients that it is a *statin‑additive* medication – not a substitute – and must be taken consistently with meals.
- Cost‑effectiveness: In real‑world registries, Vascepa’s cost per MACE prevented is comparable to high‑dose statins when target TG goals remain unmet.
- Pregnancy & Lactation: Not studied; generally avoid unless benefits outweigh unknown risks.
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• Key References
1. Bhatt DL, Steg PG, Miller M. *JAMA* 2019;321:1323‑1335 (REDUCE‑IT trial).
2. FDA approval label, 2019.
3. Lichtenstein AH, et al. *Circulation* 2020;142:e107‑e118 (guideline update).
*Prepared for medical educators and clinicians seeking a concise, reference‑friendly overview.*