ZETIA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZETIA (ZETIA).
Ezetimibe selectively inhibits the intestinal absorption of cholesterol and related phytosterols by binding to the Niemann-Pick C1-Like 1 (NPC1L1) protein on the brush border membrane of enterocytes.
| Metabolism | Ezetimibe is primarily metabolized via glucuronidation (UGT1A1, UGT1A3, UGT2B15) in the liver and intestine to its active metabolite ezetimibe-glucuronide. Both undergo enterohepatic recycling. |
| Excretion | Primarily fecal (78-85%) with minimal renal excretion (approximately 1%). |
| Half-life | Terminal elimination half-life of ezetimibe is 22 hours; ezetimibe-glucuronide has a half-life of 30 hours, allowing once-daily dosing. |
| Protein binding | Ezetimibe is >90% bound to plasma proteins. |
| Volume of Distribution | Volume of distribution is approximately 5.6 L/kg, indicating extensive extravascular distribution. |
| Bioavailability | Oral bioavailability is approximately 5.8% for ezetimibe, extensively converted to active glucuronide conjugate; systemic exposure to total ezetimibe (parent + glucuronide) is high after oral administration. |
| Onset of Action | Onset of lipid-lowering effect is approximately 2 weeks with oral administration. |
| Duration of Action | Duration of action supports once-daily dosing; maximal lipid reductions are achieved within 2 weeks and maintained with continued therapy. |
| Molecular Weight | 409.43 |
10 mg orally once daily.
| Dosage form | TABLET |
| Renal impairment | No dosage adjustment required for mild to moderate renal impairment. For severe renal impairment (GFR <30 mL/min/1.73 m²), use with caution, but no specific dose adjustment is recommended. Not studied in patients undergoing dialysis. |
| Liver impairment | Contraindicated in patients with moderate or severe hepatic impairment (Child-Pugh B or C). For mild hepatic impairment (Child-Pugh A), no dosage adjustment is required; monitor liver function tests. |
| Pediatric use | For primary hyperlipidemia (age ≥10 years): 10 mg orally once daily. Safety and efficacy not established in children <10 years. |
| Geriatric use | No specific dosage adjustment is required. Monitor renal function as elderly patients are more likely to have decreased renal function. |
| 1st trimester | No adequate studies; use only if clearly needed. May cause fetal harm based on animal studies. |
| 2nd trimester | No adequate studies; use only if clearly needed. May cause fetal harm based on animal studies. |
| 3rd trimester | No adequate studies; use only if clearly needed. May cause fetal harm based on animal studies. |
Clinical note
Comprehensive clinical and safety monograph for ZETIA (ZETIA).
| Placental transfer | Ezetimibe crosses the placenta in animal studies; human placental transfer is unknown but likely. |
| Breastfeeding | Not recommended during breastfeeding due to potential for serious adverse reactions in nursing infants. Ezetimibe is excreted in animal milk; unknown in human milk. |
| Lactation Rating |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to ezetimibe or any componentActive liver diseaseUnexplained persistent elevations in serum transaminases
| Precautions | Risk of myopathy/rhabdomyolysis, especially when combined with statins, Hepatic effects: elevation of liver enzymes; caution in patients with moderate to severe hepatic impairment, Potential for cholelithiasis (due to increased cholesterol excretion) and cholecystitis, Monitoring of liver function tests recommended before and during therapy |
| Food/Dietary | No significant food interactions. May be taken without regard to meals. Grapefruit juice does not affect ezetimibe. |
Loading safety data…
| L4 |
| Teratogenic Risk | Teratogenic Risk Profile: FDA Pregnancy Category C. In animal studies, ezetimibe was not teratogenic in rats or rabbits at doses up to 1500 mg/kg/day (≥10 times the human exposure at the clinical dose of 10 mg/day). Adequate human studies in pregnant women are lacking. No evidence of embryofetal toxicity or malformations in animal reproduction studies. In organogenesis, no increased fetal anomalies. In the third trimester, theoretical risk of reduced maternal lipid levels impacting fetal nutrition, but clinical significance unknown. Overall, use only if clearly needed. |
| Fetal Monitoring | Maternal-Fetal Monitoring: Monitor maternal lipid profiles (LDL-C, total cholesterol, triglycerides) periodically. Fetal monitoring: Routine prenatal care, ultrasound if clinically indicated for growth. Liver function tests (LFTs) as ezetimibe may cause elevations in transaminases (especially when coadministered with statins). No specific fetal monitoring required beyond standard obstetrical care. |
| Fertility Effects | Fertility Effects: No impairment of fertility observed in animal studies with ezetimibe at doses up to 1000 mg/kg/day in male or female rats. No human studies on fertility. Likely low impact on reproductive function, but insufficient data. |
| Clinical Pearls |
| Ezetimibe inhibits intestinal cholesterol absorption at the brush border via NPC1L1 transporter. It is effective as adjunct to statins for LDL-C reduction but lacks strong CV outcome data as monotherapy. May be used in sitosterolemia. Monitor LFTs when combined with statins. |
| Patient Advice | Take once daily at the same time, with or without food. · If also taking a statin, continue both unless instructed otherwise. · Report unexplained muscle pain, tenderness, or weakness, especially with statin coadministration. · Maintain a cholesterol-lowering diet while on medication. · Avoid excessive alcohol consumption. |