FULL PRESCRIBING INFORMATION
WARNING: RISK OF HEPATOTOXICITY警告：肝毒性风险
KYNAMRO can cause elevations in transaminases. In the KYNAMRO clinical trial in patients with HoFH, 4 (12%) of the 34 patients treated with KYNAMRO compared with 0% of the 17 patients treated with placebo had at least one elevation in alanine aminotransferase (ALT) ≥3x upper limit of normal (ULN). There were no concomitant clinically meaningful elevations of total bilirubin, international normalized ratio (INR) or partial thromboplastin time (PTT) [see Warnings and Precautions (5.1)].
本药可导致氨基转移酶升高。在本药的临床试验中，34名接受本药治疗纯合子型家族性高胆固醇血症(HoFH)的患者，有4名(12%)患者至少出现1次丙氨酸氨基转移酶(ALT)≥3倍正常值上限(ULN)，而17名接受安慰剂的患者无（0%）人出现。未同时出现有临床意义的总胆红素、国际标准化比值(INR)或部分凝血活酶时间(PPT)升高。
KYNAMRO also increases hepatic fat, with or without concomitant increases in transaminases. In the trials in patients with heterozygous familial hypercholesterolemia (HeFH) and hyperlipidemia, the median absolute increase in hepatic fat was 10% after 26 weeks of treatment, from 0% at baseline, measured by magnetic resonance imaging (MRI). Hepatic steatosis is a risk factor for advanced liver disease; including steatohepatitis and cirrhosis [see Warnings and Precautions (5.1)].
本药还可增加肝脏脂肪，伴或不伴氨基转移酶升高。在本药治疗杂合子型家族性高胆固醇血症(HeFH)和高脂血症的临床试验中，接受本药治疗26周后，由核磁共振成像(MRI)测定，肝脏脂肪平均绝对值由基线的0%增加至10%。肝脏脂肪变性是肝病晚期(包括脂肪肝和肝硬化)的风险因素之一。
Measure ALT, AST, alkaline phosphatase, and total bilirubin before initiating treatment and then ALT, AST regularly as recommended. During treatment, withhold the dose of KYNAMRO if the ALT or AST are ≥3 x ULN. Discontinue KYNAMRO for clinically significant liver toxicity [see Dosage and Administration (2.3) and Warnings and Precautions (5.1)].
开始治疗前应检测ALT、AST、碱性磷酸酶和总胆红素，之后建议定期检测ALT和AST。治疗期间，如ALT或AST≥3倍ULN，应暂停用药。如出现临床显著的肝毒性，应停药。
Because of the risk of hepatotoxicity, KYNAMRO is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the KYNAMRO REMS [see Warnings and Precautions (5.2)].
由于肝毒性风险，本药只能通过被称为KYNAMRO REMS计划的风险评估和减低计划(REMS)限制的计划获取。
1 INDICATIONS AND USAGE 适应症和用途
KYNAMRO TM is indicated as an adjunct to lipid-lowering medications and diet to reduce low density lipoprotein-cholesterol (LDL-C), apolipoprotein B (apo B), total cholesterol (TC), and
non-high density lipoprotein-cholesterol (non-HDL-C) in patients with homozygous familial hypercholesterolemia (HoFH).
本药作为降脂药物和饮食疗法的辅助治疗，用于纯合子型家族性高胆固醇血症(HoFH)患者，以降低低密度脂蛋白胆固醇(LDL-C)、载脂蛋白B(apo B)、总胆固醇(TC)和非高密度脂蛋白
胆固醇(non-HDL-C)。
Limitations of Use 使用限制
●The safety and effectiveness of KYNAMRO have not been established in patients with
hypercholesterolemia who do not have HoFH.
尚未建立非HoFH高胆固醇血症患者使用本药的安全性和有效性。
●The effect of KYNAMRO on cardiovascular morbidity and mortality has not been determined.
尚不确定本药对心血管病发病率和死亡率的影响。
●The safety and effectiveness of KYNAMRO as an adjunct to LDL apheresis have not been
established; therefore, the use of KYNAMRO as an adjunct to LDL apheresis is not
recommended.
尚未建立采用LDL血浆置换分离法时合用本药的安全性和有效性，故不推荐采用LDL 血浆置换分离法时合用本药。
2 DOSAGE AND ADMINISTRATION 用法用量
2.1 General Dosing Information 一般给药信息
Before beginning treatment with KYNAMRO, measure transaminases (ALT, AST), alkaline phosphatase, and total bilirubin [see Warnings and Precautions (5.1)].
开始治疗前应检测ALT、AST、碱性磷酸酶和总胆红素。
The recommended dose of KYNAMRO is 200 milligrams (mg) once weekly as a subcutaneous injection.
本药的推荐剂量为一次200mg，一周1次，皮下注射。
KYNAMRO is intended for subcutaneous use only. Do not administer intramuscularly or intravenously.
本药仅用于皮下注射，禁止肌内或静脉注射。
The injection should be given on the same day every week, but if a dose is missed, the injection should be given at least 3 days from the next weekly dose
注射应于每周同一日进行，但如错过用药时间，应于下一剂量至少3日前注射。
After initiation of KYNAMRO therapy lipid levels should be monitored at least every 3 months for the first year. Maximal reduction of LDL-C may be seen with KYNAMRO therapy after approximately 6 months (based on the time to steady state seen in clinical studies). Health care providers should assess the patient’s LDL-C level after 6 months to determine if the LDL-C reduction achieved with KYNAMRO is sufficiently robust to warrant the potential risk of liver toxicity.
开始治疗后第1年，应至少每3个月检测血脂水平。用药6个月后LDL-C可降至最低水平(基于临床试验稳定状态时间)，故用药6个月后应评估患者LDL-C水平，确定LDL-C降低是否足够确定肝毒性的潜在风险。
2.2 Administration 给药方法
Each vial or pre-filled syringe of KYNAMRO provides 200 mg of mipomersen sodium in a deliverable volume of 1 milliliter (mL) of solution and is intended for single-use only.
每小瓶或预填充注射器中含200mg(即1ml溶液)米泊美生钠，仅供一次性使用。
The KYNAMRO vial or pre-filled syringe should be removed from 2-8°C (36-46°F) refrigerated storage and allowed to reach room temperature for at least 30 minutes prior to administration.
用药前，应将本药小瓶或填充注射器从2-8℃冷藏环境中取出，并于用药前30分钟置于室温。Parenteral drug products should be inspected visually prior to administration. If the solution is cloudy or contains visible particulate matter, the contents must not be injected and the product should be returned to the pharmacy.
