EZETIMIBE
Clinical safety rating: safe
Animal studies have demonstrated safety
Inhibits Niemann-Pick C1-Like 1 (NPC1L1) protein in the small intestine, reducing intestinal absorption of dietary and biliary cholesterol, leading to decreased hepatic cholesterol stores and increased clearance of cholesterol from the blood.
| Metabolism | Primarily metabolized via glucuronidation by UGT1A1, UGT1A3, and UGT2B15; minimal CYP450 involvement (negligible oxidative metabolism). Ezetimibe and ezetimibe-glucuronide undergo enterohepatic recycling. Elimination is via biliary and fecal routes; renal excretion is minimal. |
| Excretion | Biliary and fecal: ~78% as parent compound; renal: ~11% as metabolite; enterohepatic recirculation occurs. |
| Half-life | Approximately 22 hours for ezetimibe and its active glucuronide metabolite; steady-state achieved within 3-7 days. |
| Protein binding | >99.7% bound to human plasma proteins, primarily albumin. |
| Volume of Distribution | Not applicable; ezetimibe has a Vd of approximately 18 L/kg due to extensive tissue distribution, but clinical relevance is limited. |
| Bioavailability | Oral: variable; estimated ~35-65% due to extensive glucuronidation and enterohepatic recycling. |
| Onset of Action | Oral: reduction in LDL-C observed within 2 weeks; maximal effect by 4-6 weeks. |
| Duration of Action | LDL-C lowering persists for duration of therapy; effects wane over 2-3 weeks after discontinuation. |
10 mg orally once daily, with or without food, at any time of day.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for any degree of renal impairment including end-stage renal disease. |
| Liver impairment | Contraindicated in patients with moderate (Child-Pugh B) to severe (Child-Pugh C) hepatic impairment. Use with caution in mild hepatic impairment without clear dose recommendations. |
| Pediatric use | Children ≥10 years: 10 mg orally once daily. Children <10 years: safety and efficacy not established; use not recommended. |
| Geriatric use | No specific dose adjustment needed. Use standard adult dosing based on clinical studies including patients >65 years. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Cholestyramine decreases ezetimibe levels Fibrates may increase the risk of cholelithiasis.
| Breastfeeding | Unknown if excreted in human breast milk; no data on M/P ratio. Due to potential for serious adverse reactions in nursing infants, decision should be made to discontinue nursing or drug, considering importance of drug to mother. |
| Teratogenic Risk | Insufficient human data; animal studies show no evidence of teratogenicity at clinically relevant doses. FDA Pregnancy Category C. No known risk of congenital anomalies based on limited data, but cannot exclude risk; avoid use in first trimester unless clearly needed. |
■ FDA Black Box Warning
None.
| Common Effects | Diarrhea |
| Serious Effects |
["Hypersensitivity to ezetimibe or any component of the formulation.","Active liver disease or unexplained persistent elevations in serum transaminases (when used with a statin).","Coadministration with a statin in pregnant or nursing women (relative contraindication)."]
| Precautions | ["Hepatic impairment: Not recommended in moderate to severe liver dysfunction; monitor liver enzymes when coadministered with statins or fenofibrate.","Myopathy/Rhabdomyolysis: Increased risk when used with statins, especially at higher doses; caution in patients with predisposing factors (e.g., renal impairment, hypothyroidism).","Pancreatitis: Rare cases reported, especially with concomitant fenofibrate.","Cholelithiasis: May increase cholesterol secretion into bile, potentially causing gallstones; use caution in patients with biliary obstruction.","Hypersensitivity: Monitor for allergic reactions (e.g., angioedema, rash, urticaria).","Fetal risk: Use only if clearly needed in pregnancy (Category C); discontinue nursing or drug in lactating women.","Pediatric use: Safety and efficacy established in adolescents (≥10 years) for HoFH and sitosterolemia; not recommended for primary hyperlipidemia in pediatric patients <10 years."] |
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| Fetal Monitoring |
| No specific fetal monitoring required. Monitor maternal hepatic function and lipid profiles periodically. |
| Fertility Effects | No significant effects on fertility reported in animal studies; human data insufficient. |