Generic Name

Zetia (ezetimibe)

Mechanism

• Selective inhibitor of the Niemann–Pick C1‑like 1 (NPC1L1) transporter on enterocytes.
• Prevents uptake of micellar cholesterol → ↓ intestinal absorption → ↓ plasma LDL‑c.
• Minimal hepatic synthesis inhibition → low interaction risk with statins.

Pharmacokinetics

• Absorption: 100 % oral bioavailability; peak plasma concentrations at ~4 h.
• Distribution: 94 % protein‑bound; total body clearance low (~1 L/h).
• Metabolism: Primarily glucuronidation (UGT1A4, UGT2B7); minor CYP3A4 involvement.
• Elimination: Mainly fecal (~70 %) and renal (~16 %).
• Half‑life: 22 h; steady state in ~4 days.
• Drug interactions: Low propensity; caution with potent CYP3A4 inhibitors/inducers that may affect statins.

Indications

• Primary hypercholesterolemia (heterozygous familial or familial combined) – monotherapy or adjunct to statins.
• Mixed dyslipidemia – add‑on to statin therapy when LDL‑c goals unmet.
• Lifestyle‑induced hyperlipidemia – when diet/exercise insufficient.

Contraindications

• Contraindicated: Pregnant or lactating women; hypersensitivity to ezetimibe or any component.
• Warnings:
• Liver function monitoring in patients on concomitant statins, especially in uncontrolled liver disease.
• Renal impairment: No dose adjustment required, but caution in severe CKD due to minimal excretion.
• Precautions:
• Use cautiously in patients with absorption disorders (e.g., celiac disease).
• Not recommended as first‑line monotherapy in patients with statin intolerance only if benefit outweighs safety.

Dosing

• Start with low‑dose statin + ezetimibe when target LDL‑c is far below goal to rapidly achieve control.
• Discontinue in pregnancy or if INR > 3.0.

Adverse Effects

• Common (≤10 %):
• Headache, abdominal pain, musculoskeletal pain, myalgia, mild serum‐creatinine elevation.
• Serious (≤1 %):
• Statin‑related myopathy (speak‑to‑the‑team) if combined with high‑dose statins.
• Rare hepatic transaminase elevation (monitor LFTs initially).

Monitoring

• Baseline & 4‑6 weeks:
• Liver enzymes (AST/ALT), CK, total cholesterol, LDL‑c, HDL‑c, triglycerides.
• Follow‑up:
• Every 3 months after achieving LDL‑c target; adjust if >3 × baseline ALT/AST.
• Renal function: Check eGFR at baseline and annually if CKD present.

Clinical Pearls

• Synergy with Statins: Ezetimibe + statin often achieves LDL‑c goals faster than escalating statin dose alone, reducing myopathy risk.
• “Statin‑Intolerance” Alternative: Use ezetimibe monotherapy in patients who cannot tolerate any statin (but it still requires monitoring due to occasional myalgias).
• Cardiovascular Outcomes: Large trials (e.g., IMPROVE‑IT) demonstrate mortality benefit when ezetimibe added to statin therapy in post‑ACS patients.
• Pediatric Use: Approved for heterozygous familial hypercholesterolemia in children ≥8 yrs when diet/other drugs ineffective; start at 10 mg daily.
• Drug‑Drug Interaction Tip: Co‑administration with potent CYP3A4 inhibitors (ketoconazole) may increase statin levels—monitor for myopathy.
• Practical Tip: Patients may experience tasting or mild GI discomfort; advise taking with a light meal.

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• *For a deeper dive, reference the latest AHA/ACC lipid guideline updates and the FDA prescribing information for Zetia.*