Indication and Important Safety Information
JUXTAPID is used along with a low-fat diet and other lipid-lowering treatments, including LDL apheresis where available, in people with HoFH. It is not known whether JUXTAPID can decrease problems from high cholesterol, such as heart attack, stroke, death or other health problems. It is also not known whether Juxtapid is safe for use in people with high cholesterol but who do not have HoFH.
IMPORTANT SAFETY INFORMATION
JUXTAPID can cause serious side effects, including liver problems. For this reason, your doctor should do blood tests to check your liver before you start JUXTAPID, if your dose is increased, and while you take JUXTAPID. If your tests show some liver problems, your doctor may adjust your dose of JUXTAPID or stop it altogether.
You should tell your doctor if you have had liver problems, including liver problems while taking other medicines.
JUXTAPID is available only through certified pharmacies that are enrolled in the JUXTAPID REMS Program. Your doctor must be enrolled and certified in the program in order for you to be prescribed JUXTAPID.
You should not take JUXTAPID if:
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You are pregnant
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You are taking medications known as moderate or strong CYP3A4 inhibitors, which affect how the body breaks down JUXTAPID
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You have moderate or severe liver problems or active liver disease, including elevated liver function tests
JUXTAPID may cause harm to your unborn baby. If you are pregnant, think you may be pregnant, or are planning to become pregnant, do not take JUXTAPID. Do not have sex while taking JUXTAPID unless you are using effective birth control. If you become pregnant while taking JUXTAPID, stop taking JUXTAPID and call your doctor right away.
Diarrhea, nausea/vomiting, and stomach pain/discomfort are very common with JUXTAPID. Strictly following a low-fat diet may help lower the chance of having these symptoms. These side effects can also be symptoms of liver problems. Tell your doctor right away if you have any of these symptoms of liver problems while taking JUXTAPID: nausea; vomiting or stomach pain that gets worse, does not go away, or changes; fever; yellowing of your eyes or skin; feeling more tired than usual; having flu-like symptoms.
JUXTAPID makes it harder for some nutrients to get into your body. Take Vitamin E and fatty acids each day while you take JUXTAPID. Ask your doctor, nurse, or dietician how to add them to your diet.
The most common side effects of JUXTAPID include diarrhea (loose stool),
nausea, vomiting, stomach cramping or pain, indigestion, and gas. Tell your doctor if you have any side effect that bothers you or that does not go away.
These are not all the possible side effects of JUXTAPID. For more information, ask your doctor or pharmacist.
Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. JUXTAPID may affect the way other medicines work, and other medicines may affect how JUXTAPID works. You should not drink grapefruit juice while taking JUXTAPID.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.
美国食品药品管理局(FDA)已批准了Juxtapid(lomitapide)作为低脂饮食和其他降血脂治疗的辅助药物，用于降低纯合子家族性高胆固醇血症(HoFH)患者低密度脂蛋白胆固醇(LDL-C)、总胆固醇、载脂蛋白B和非高密度脂蛋白胆固醇(非-HDL)。Juxtapid是一种微粒体甘油三酯转运蛋白抑制剂。
FDA批准Juxtapid是基于一项关键性3期研究结果。该研究评价了29例HoFH患者服用Juxtapid降低LDL-C水平的有效性和安全性，是一项为期78周的国际多中心、单组、开放性研究，其结果发表于《柳叶刀》杂志。在这项研究中，Juxtapid初始治疗剂量为每天5 mg，基于耐受性和可接受的肝酶水平，剂量逐渐增加至10 mg、20 mg、40 mg和 60 mg。
在现有降血脂治疗的Juxtapid添加治疗中，意向治疗患者平均LDL-C水平由基线时的336 mg/dL 显著降至26周时的190 mg/dl(降低40%)，其中提前终止治疗患者采取末期观察推进法评估。23例完成26周研究患者LDL-C水平平均降低50%。在26周后的安全性评价阶段，允许调整同期降脂治疗。在长期治疗阶段，LDL-C平均降低幅度仍能维持。
该研究最常见不良反应是胃肠道反应，在29例患者中有27例(93%)报告出现胃肠道反应。28%的患者报告的不良反应包括腹泻、恶心、呕吐、消化不良和腹痛。其他常见不良反应有体重下降、腹部不适、腹胀、便秘、胃肠气胀、胸痛、流感、鼻咽炎和疲乏。还观察到肝酶水平和肝脏脂肪升高。
由于肝脏毒性风险，根据风险评估和降低策略，Juxtapid的使用将受到限制。在治疗开始之前，应检测肝脏转氨酶、碱性磷酸酶和总胆红素水平，并应定期监测丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)。治疗期间，如果ALT或AST水平≥ 3倍正常值最高上限，应调整Juxtapid剂量。一旦出现有临床意义的肝脏毒性，应停止使用Juxtapid。
考虑到Juxtapid作用于小肠，可能会减少脂溶性营养成分的吸收。接受Juxtapid治疗的患者应每天服用含有400 IU的维生素E和至少200 mg亚油酸、210 mg α-亚麻酸、110 mg EPA以及80 mg DHA的补充剂。
Juxtapid用于非HoFH高脂血症患者的安全性和有效性尚未确定。
http://www.juxtapid.com/
Lojuxta : EPAR - Procedural steps taken and scientific information after authorisation
Lojuxta : EPAR - Public assessment report
