近日，美国食品和药物管理局（FDA）已批准Juxtapid(lomitapide)，作为低脂饮食和其他降脂治疗的辅助药物，包括低密度脂蛋白单采，以降低纯合家族性高胆固醇血症（HoFH）患者的低密度脂素胆固醇（LDL-C）、总胆固醇（TC）、载脂蛋白B（apo B）和非高密度脂蛋白胆固醇（non-HDL）。
HoFH是一种严重、罕见的遗传性疾病，会损害负责从体内清除LDL-C（“坏”胆固醇）的受体的功能。低密度脂蛋白受体功能的丧失会导致血液胆固醇水平的极度升高。HoFH患者经常发展为过早和进行性动脉粥样硬化，即动脉狭窄或阻塞。 
批准日期：2012年12月21日 公司：Aegerion's
JUXTAPID（甲磺酸洛美他派[lomitapide]）胶囊，用于口服
美国最初批准：2012年
警告：肝毒性风险请参见完整的BOXED警告的完整预定信息。
JUXTAPID可导致转氨酶升高。
在开始治疗前测量丙氨酸和天冬氨酸氨基转移酶（ALT，AST），碱性磷酸酶和总胆红素，然后按照建议定期测定ALT和AST。
在治疗期间，如果ALT或AST≥正常上限（ULN）的3倍，则调整JUXTAPID的剂量。
停止JUXTAPID治疗临床显着的肝毒性。
JUXTAPID增加肝脏脂肪（肝脂肪变性），伴随或不伴随转氨酶升高。
与JUXTAPID相关的肝脏脂肪变性可能是进行性肝病的危险因素，包括脂肪性肝炎和肝硬化。
由于存在肝毒性风险，JUXTAPID只能通过称为JUXTAPID REMS计划的受限程序获得。仅对具有与HoFH一致的临床或实验室诊断的患者开JUXTAPID。JUXTAPID的安全性和有效性尚未确定为没有HoFH的高胆固醇血症患者。
作用机制
JUXTAPID直接结合并抑制微粒体甘油三酯转运蛋白（MTP），其存在于内质网的腔中，从而阻止含有apo B的脂蛋白在肠细胞和肝细胞中的组装。 这抑制了乳糜微粒和VLDL的合成。 抑制VLDL的合成导致血浆LDL-C水平降低。
适应症和用法
JUXTAPID是一种微粒体甘油三酯转运蛋白抑制剂，可作为低脂饮食和其他降脂治疗的辅助手段，包括可用的LDL血浆置换，以降低低密度脂蛋白胆固醇（LDL-C），总胆固醇（TC），载脂蛋白B（apo B）和纯合子家族性高胆固醇血症（HoFH）患者的非高密度脂蛋白胆固醇（非HDL-C）。
使用限制
JUXTAPID的安全性和有效性尚未确定在没有HoFH的高胆固醇血症患者中，包括那些患有杂合子家族性高胆固醇血症（HeFH）的患者。
JUXTAPID对心血管疾病发病率和死亡率的影响尚未确定。
剂量和给药
治疗前，测量ALT，AST，碱性磷酸酶和总胆红素;对有生育潜力的女性进行阴性妊娠试验;并开始低脂饮食，从脂肪中提供<20％的能量。
每天一次以5毫克开始治疗。基于可接受的安全性/耐受性的滴定剂量：在至少2周后每天增加至10mg;然后，至少每隔4周，至20毫克，40毫克，最高推荐剂量为每天60毫克。
由于脂溶性维生素/脂肪酸的吸收减少：每日服用维生素E，亚油酸，α-亚麻酸（ALA），二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）补充剂。
每天吃一次，整个，用水和不含食物，晚餐后至少2小时。
透析或基线轻度肝功能损害的终末期肾病患者每日不应超过40毫克。
剂量形式和强度
胶囊：5mg，10mg，20mg，30mg，40mg和60mg。
禁忌症
怀孕。
与强或中等CYP3A4抑制剂同时使用。
中度或重度肝功能损害或活动性肝病，包括不明原因的持续异常肝功能检查。
警告和注意事项
胚胎 - 胎儿毒性：生育潜力的女性在开始JUXTAPID之前应进行阴性妊娠试验，并在治疗期间使用避孕措施。
93％的患者出现胃肠道不良反应，并可能影响伴随口服药物的吸收。
不良反应
最常见的不良反应（发生率≥28％）是腹泻，恶心，呕吐，消化不良和腹痛。
要报告疑似不良反应，请致电1-855-303-2347联系Aegerion Pharmaceuticals或1-800-FDA-1088或www.fda.gov/medwatch联系FDA。
药物相互作用
CYP3A4抑制剂增加了对lomitapide的暴露。强力和中度CYP3A4抑制剂禁用JUXTAPID。患者必须避免使用葡萄柚汁。
当给予弱CYP3A4抑制剂时，JUXTAPID的剂量应减少一半。然后可以将JUXTAPID的剂量上调至每日30mg的最大推荐剂量。
华法林：Lomitapide增加华法林的血浆浓度。定期监测国际标准化比率（INR），尤其是JUXTAPID剂量调整。
辛伐他汀和洛伐他汀暴露随着JUXTAPID的增加而增加。由于肌病风险，与JUXTAPID共同给药时限制剂量。
P-糖蛋白（P-gp）底物：考虑到P-gp底物的剂量减少，因为JUXTAPID可能增加吸收。
胆汁酸螯合剂：将JUXTAPID剂量分开至少4小时。
用于特定人群
护理母亲：停止使用药物或护理。
儿科患者：未建立安全性和有效性
包装提供/存储和处理
5毫克胶囊：
橙色/橙色硬明胶胶囊，印有黑色墨水“A733”和“5毫克”
瓶子28 NDC 76431-105-01
10毫克胶囊：
橙色/白色硬明胶胶囊，印有黑色墨水“A733”和“10毫克”
瓶子28 NDC 76431-110-01
20毫克胶囊：
白色/白色硬明胶胶囊，印有黑色墨水“A733”和“20毫克”
瓶子28 NDC 76431-120-01
30毫克胶囊：
橙色/黄色硬明胶胶囊，印有黑色墨水“A733”和“30毫克”
瓶子28 NDC 76431-130-01
40毫克胶囊：
黄色/白色硬明胶胶囊，印有黑色墨水“A733”和“40毫克”
瓶子28 NDC 76431-140-01
60毫克胶囊：
黄色/黄色硬明胶胶囊，印有黑色墨水“A733”和“60毫克”
瓶子28 NDC 76431-160-01
储存：储存在20°C至25°C（68°F至77°F）;允许的偏差在15°C至30°C之间（59°F至86°F之间）。如果平均动力学温度不超过25°C（77°F），可以容忍短暂暴露在高达40°C（104°F）的温度;但是，应尽量减少这种暴露。保持容器紧关闭并防止受潮。
完整说明资料附件：
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e4c45bb5-15f4-437e-ab98-a649b3676d14
JUXTAPID® (lomitapide) capsules, for oral use
IMPORTANT SAFETY INFORMATION
WARNING: RISK OF HEPATOTOXICITY
JUXTAPID can cause elevations in transaminases. In the JUXTAPID clinical trial, 10 (34%) of the 29 patients treated with JUXTAPID had at least one elevation in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥3x upper limit of normal (ULN). There were no concomitant clinically meaningful elevations of total bilirubin, international normalized ratio (INR), or alkaline phosphatase.
JUXTAPID also increases hepatic fat, with or without concomitant increases in transaminases. The median absolute increase in hepatic fat was 6% after both 26 and 78 weeks of treatment, from 1% at baseline, measured by magnetic resonance spectroscopy. Hepatic steatosis associated with JUXTAPID treatment may be a risk factor for progressive liver disease, including steatohepatitis and cirrhosis.
Measure ALT, AST, alkaline phosphatase, and total bilirubin before initiating treatment and then ALT and AST regularly as recommended. During treatment, adjust the dose of JUXTAPID if the ALT or AST are ≥3x ULN. Discontinue JUXTAPID for clinically significant liver toxicity.
Because of the risk of hepatotoxicity, JUXTAPID is available only through a restricted program under a Risk eva luation and Mitigation Strategy (REMS) called the JUXTAPID REMS PROGRAM.
CONTRAINDICATIONS
Pregnancy
Concomitant administration of moderate or strong CYP3A4 inhibitors
Moderate or severe hepatic impairment or active liver disease including unexplained persistent elevations of serum transaminases
WARNINGS AND PRECAUTIONS
JUXTAPID can cause elevations in transaminases and hepatic steatosis. Although cases of hepatic failure have not been reported, there is concern that JUXTAPID could induce steatohepatitis, which can progress to cirrhosis over several years. Modify the dose of JUXTAPID if elevations of transaminases are observed and discontinue JUXTAPID for persistent or clinically significant elevations. If transaminase elevations are accompanied by clinical symptoms of liver injury, such as nausea, vomiting, abdominal pain, fever, jaundice, lethargy, flu-like-symptoms, increases in bilirubin ≥2x ULN, or active liver disease, discontinue treatment with JUXTAPID and identify the probable cause. Use JUXTAPID with caution when co-administered with agents known to be hepatotoxic. Alcohol may increase levels of hepatic fat and induce or exacerbate liver injury.
Measure ALT, AST, alkaline phosphatase, and total bilirubin before initiating treatment. During the first year, measure liver-related tests (ALT and AST, at a minimum) prior to each increase in dose or monthly, whichever occurs first. After the first year, do these tests at least every 3 months and before any increase in dose.
Females of reproductive potential should have a negative pregnancy test before starting JUXTAPID and should use effective contraception during therapy with JUXTAPID.
Given its mechanism of action in the small intestine, JUXTAPID may reduce the absorption of fat-soluble nutrients. Patients treated with JUXTAPID should take daily supplements that contain 400 international units vitamin E and at least 200 mg linoleic acid, 210 mg alpha-linolenic acid (ALA), 110 mg eicosapentaenoic acid (EPA), and 80 mg docosahexaenoic acid (DHA).
Gastrointestinal adverse reactions are common and may lead to treatment discontinuation. To reduce the risk of gastrointestinal adverse reactions, patients should adhere to a low-fat diet supplying less than 20% of energy from fat and the dosage of JUXTAPID should be increased gradually.
Combination with CYP3A4 inhibitors increases exposure to lomitapide. Strong and moderate CYP3A4 inhibitors should not be used with JUXTAPID. JUXTAPID dosage should not exceed 30 mg daily when used concomitantly with weak CYP3A4 inhibitors.
Due to risk of myopathy associated with simvastatin or lovastatin, doses of these agents should be limited when co-administered with JUXTAPID.
JUXTAPID increases the plasma concentrations of warfarin. Increases or decreases in the dose of JUXTAPID may lead to supra- or subtherapeutic anticoagulation, respectively. Patients taking warfarin should undergo regular monitoring of the INR, especially after any changes in JUXTAPID dosage.
Avoid use of JUXTAPID in patients with rare hereditary disorders of galactose intolerance.
ADVERSE REACTIONS
The most common adverse reactions were gastrointestinal, reported by 27 (93%) of 29 patients. Adverse reactions reported by ≥8 (28%) or more patients in the HoFH clinical trial included diarrhea, nausea, vomiting, dyspepsia and abdominal pain. Other common adverse reactions, reported by 5 to 7 (17-24%) patients, included weight loss, abdominal discomfort, abdominal distension, constipation, flatulence, increased ALT, chest pain, influenza, nasopharyngitis, and fatigue.