Davis Kyle A, Miyares Marta A
Kyle A. Davis, Pharm.D., BCPS, is Clinical Hospital Pharmacist-Internal Medicine; and Marta A. Miyares, Pharm.D., BCPS (AQ-Cardiology), CACP, is Clinical Hospital Pharmacist-Internal Medicine, Jackson Memorial Hospital, Miami, FL.
Am J Health Syst Pharm. 2014 Jun 15;71(12):1001-8. doi: 10.2146/ajhp130592.
The pharmacology, pharmacokinetics, and clinical efficacy and safety of lomitapide in the management of homozygous familial hypercholesterolemia (HoFH) are reviewed.
Lomitapide (Juxtapid, Aegerion Pharmaceuticals) is an oral microsomal triglyceride transfer protein (MTP) inhibitor indicated for the treatment of patients with HoFH, a rare form of hypercholesterolemia that can lead to premature atherosclerotic disease. In clinical trials, the use of lomitapide alone or in combination with other lipid-lowering modalities reduced plasma concentrations of low-density lipoprotein cholesterol (LDL-C) by a mean of more than 50%. Lomitapide is associated with significant gastrointestinal adverse effects and increases in hepatic fat levels. Lomitapide undergoes hepatic metabolism via cytochrome P-450 (CYP) isoenzyme 3A4 and interacts with CYP3A4 substrates including atorvastatin and simvastatin; dose adjustment is recommended when lomitapide is used concurrently with these agents. In patients receiving concomitant warfarin, the International Normalized Ratio (INR) should be closely monitored, as lomitapide use may increase INR values. The recommended initial dosage of lomitapide is 5 mg once daily, with subsequent upward dose adjustment at specified intervals according to tolerability. Lomitapide is contraindicated in patients with moderate-to-severe liver disease, patients with sustained abnormal liver function tests, patients taking strong or moderate CYP3A4 inhibitors, and pregnant patients.
Lomitapide is an oral MTP inhibitor approved for the treatment of HoFH. This agent appears to be a realistic option for patients with HoFH who are unable to attain their LDL-C goal or cannot tolerate statin therapy.
综述洛美他派在纯合子家族性高胆固醇血症（HoFH）治疗中的药理学、药代动力学、临床疗效及安全性。
洛美他派（Juxtapid，Aegerion制药公司）是一种口服微粒体甘油三酯转移蛋白（MTP）抑制剂，用于治疗HoFH患者，HoFH是一种罕见的高胆固醇血症，可导致过早的动脉粥样硬化疾病。在临床试验中，单独使用洛美他派或与其他降脂方法联合使用可使低密度脂蛋白胆固醇（LDL-C）血浆浓度平均降低超过50%。洛美他派与显著的胃肠道不良反应及肝脏脂肪水平升高有关。洛美他派通过细胞色素P-450（CYP）同工酶3A4进行肝脏代谢，并与包括阿托伐他汀和辛伐他汀在内的CYP3A4底物相互作用；当洛美他派与这些药物同时使用时，建议调整剂量。在接受华法林治疗的患者中，应密切监测国际标准化比值（INR），因为使用洛美他派可能会增加INR值。洛美他派的推荐初始剂量为每日一次5mg，随后根据耐受性在特定间隔进行剂量上调调整。中度至重度肝病患者、肝功能检查持续异常的患者、服用强效或中度CYP3A4抑制剂的患者以及孕妇禁用洛美他派。
洛美他派是一种口服MTP抑制剂，被批准用于治疗HoFH。对于无法实现LDL-C目标或无法耐受他汀类药物治疗的HoFH患者，该药似乎是一个切实可行的选择。
