EZETIMIBE
Clinical safety rating
safeAnimal 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. |
| Molecular Weight | 409.43 |
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 | Limited human data; animal studies show no teratogenicity at clinically relevant doses. Use only if clearly needed. |
| 2nd trimester | No well-controlled human studies; potential for decreased fetal cholesterol synthesis. Use only if benefit outweighs risk. |
| 3rd trimester | May reduce fetal cholesterol synthesis; avoid use unless absolutely necessary. |
Clinical note
Cholestyramine decreases ezetimibe levels Fibrates may increase the risk of cholelithiasis.
| Placental transfer | Transfers across placenta in animal studies; human data limited but expected to cross due to molecular weight and lipophilicity. |
| Breastfeeding | Ezetimibe is present in human milk at low levels; clinical significance unknown. Caution is advised due to potential for disruption of infant lipid metabolism. |
| Lactation Rating | L3 (Moderately Safe) |
| 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. |
| 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. |
■ FDA Black Box Warning
None.
| Common Effects | Diarrhea |
| Serious Effects |
Hypersensitivity to ezetimibe or any componentModerate to severe hepatic impairment (Child-Pugh B or C)Concurrent use with a statin in patients with active liver disease or unexplained persistent transaminase elevations
| 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. |
| Food/Dietary | No significant food interactions. Avoid high-fat meals if combined with statins (to minimize statin-related myopathy risk). Bile acid sequestrants (e.g., cholestyramine) should be taken at least 4 hours before or 2 hours after ezetimibe to reduce absorption interference. |
| Clinical Pearls | Ezetimibe inhibits intestinal absorption of cholesterol via the Niemann-Pick C1-like 1 (NPC1L1) protein. It is often used as adjunctive therapy to statins for LDL-C lowering. Unlike statins, it does not affect hepatic HMG-CoA reductase and has minimal drug interactions, making it useful for statin-intolerant patients. It can be combined with fenofibrate but caution with gemfibrozil due to increased risk of cholelithiasis. Contraindicated in active liver disease or unexplained persistent transaminase elevations. No dose adjustment needed in chronic kidney disease. |
| Patient Advice | Take ezetimibe exactly as prescribed, usually once daily with or without food. · It is usually taken in addition to a statin or other cholesterol-lowering medications. · You may experience mild side effects such as diarrhea, joint pain, or upper respiratory infection. · Rarely, serious muscle pain or liver problems can occur; report unexplained muscle aches, tenderness, or weakness, especially if accompanied by fever or dark urine. · Keep taking the medication even if you feel well, as high cholesterol has no symptoms. · Do not stop or change your dose without discussing with your doctor. · Inform your healthcare provider about all other medications, especially bile acid sequestrants (e.g., cholestyramine) which may reduce ezetimibe absorption. · Pregnancy and breastfeeding: Use only if clearly needed; discuss with your doctor. |
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