⽶泊美⽣钠注射液
KYNAMRO（mipomernsodium）FDA药品说明书翻译FULL PRESCRIBING INFORMATION
WARNING: RISK OF HEPATOTOXICITY警告：肝毒性风险
KYNAMRO can cau elevations in transaminas. 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 aminotransfera (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) [e 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 increas hepatic fat, with or without concomitant increas in transaminas. In the trials in patients with heterozygous familial hypercholesterolemia (HeFH) and hyperlipidemia, the medi
an absolute increa in hepatic fat was 10% after 26 weeks of treatment, from 0% at baline, measured by magnetic resonance imaging (MRI). Hepatic steatosis is a risk factor for advanced liver dia; including steatohepatitis and cirrhosis [e 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 phosphata, and total bilirubin before initiating treatment and then ALT, AST regularly as recommended. During treatment, withhold the do of KYNAMRO if the ALT or AST are ≥3 x ULN. Discontinue KYNAMRO for clinically significant liver toxicity [e 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。admit的用法
Becau 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 [e 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acknowledgement
授首
胆固醇(non-HDL-C)。
Limitations of U 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 u 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 transaminas (ALT, AST), alkaline phosphata, and total bilirubin [e 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 do 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 u 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 do is misd, the injection should be given at least 3 days from the next weekly do
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 en with KYNAMRO therapy after approximately 6 months (bad on the time to steady state en in clinical studies). Health care providers should ass
ess 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 mipomern sodium in a deliverable volume of 1 milliliter (mL) of solution and is intended for single-u 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 ret
urned to the pharmacy.
夜雨寄北翻译
⽤药前应⽬测检查，如溶液浑浊或含颗粒物，不得注射，并将产品退回药房。
The first injection administered by the patient or caregiver should be performed under the guidance and supervision of an appropriately qualified health care professional.
患者或护理⼈员的初次注射应在专业⼈⼠的指导和监督下进⾏。
KYNAMRO should be injected into the abdomen, thigh region, or outer area of the upper arm. KYNAMRO should not be injected in areas of active skin dia or injury such as sunburns, skin rashes, inflammation, skin infections, active areas of psoriasis, etc. Areas of tattooed skin and scarring should also be avoided.
本药可于腹部、⼤腿、上臂外侧注射。不得于活动性⽪肤病或损伤处注射，如晒伤、⽪疹、炎症、⽪肤感染、银屑病活动区域，也应避免在纹⾝或结疤部位注射。
2.3 Adjustments for Patients Developing Transamina Elevations 氨基转移酶升⾼患者剂量调整
Table 1 summarizes recommendations for monitoring for patients who develop elevated transaminas during therapy with KYNAMRO [e Warnings and Precautions (5.1)].
对于接受本药治疗期间氨基转移酶升⾼的患者，剂量调整建议见表1。
Table 1: Monitoring for Patients With Elevated Transaminas
表1：氨基转移酶升⾼患者监测
ALT OR AST ALT或AST TREATMENT AND MONITORING RECOMMENDATIONS* 治疗和监测建议
≥3x and < 5x ULN ALT或AST≥3倍ULN，且＜5倍ULN ●Confirm elevation with a repeat measurement within one week.
⼀周内复查以确定是否升⾼。
●If confirmed, withhold dosing, obtain additional liver-related tests
if not already measured (such as total bilirubin, alkaline
phosphata and INR) and investigate to identify the probable
cau.
若确定，暂停⽤药并进⾏其他的肝脏相关试验(如碱性磷酸酶、总胆红素和INR)，并调查升⾼的可能原因。motel
●If resuming KYNAMRO after transaminas resolve to <3x ULN
consider monitoring liver-related tests more frequently.
如氨基转移酶降低⾄＜3倍ULN，可恢复给药，更频繁地监测肝脏相关检查。
≥5x ULN
ALT或AST≥5倍ULN ●Withhold dosing, obtain additional liver-related tests if not already
measured (such as total bilirubin, alkaline phosphata and INR) and investigate to identify the probable cau.
暂停⽤药，并进⾏其他的肝脏相关试验(如碱性磷酸酶、总胆红素和INR)，并调查以确定可能的原因。
●If resuming KYNAMRO after transaminas resolve to < 3x ULN,
monitor liver-related tests more frequently.
如氨基转移酶降低⾄＜3倍ULN，可恢复给药，更频繁地监测肝脏相关检查。
* Recommendations bad on an ULN of approximately 30-40 international units/L.
建议基于ULN约为30-40U/L。
If transamina elevations are accompanied by clinical symptoms of liver injury (e.g., naua, vomiting, abdominal pain, fever, jaundice, lethargy, flu-like sy mptoms), increas in bilirubin ≥2x ULN, or active liver dia, discontinue treatment with KYNAMRO and investigate to identify the
probable cau [e Warnings and Precautions (5.1)].
转移酶升⾼并伴有肝损害的临床症状(如恶⼼、呕吐、腹痛、发热、黄疸、嗜睡、流感样症状)、胆红素≥2倍ULN或活动性肝病，应停⽤本药并调查以确定可能的原因。
3 DOSAGE FORMS AND STRENGTHS 剂型和规格
●Single-u vial containing 1 mL of a 200 mg/mL clear, colorless to slightly yellow solution.
⼀次性使⽤⼩瓶内为澄清、⽆⾊或淡黄⾊溶液，1ml/瓶，200mg/ml。
●Single-u pre-filled syringe containing 1 mL of a 200 mg/mL clear, colorless to slightly
yellow solution.
⼀次性使⽤预填充注射器内为澄清、⽆⾊或淡黄⾊溶液，1ml/⽀，200mg/ml。
4 CONTRAINDICATIONS 禁忌症innocence歌词翻译
KYNAMRO is contraindicated in the following conditions: 本药禁⽤于以下情况：
●Moderate or vere hepatic impairment (Child-Pugh B or C) or active liver dia, including
unexplained persistent elevations of rum transaminas [e Warnings and Precautions (5.1) and U in Specific Populations (8.8)]
中⾄重度肝损伤(Child-Pugh分级为B级或C级)患者、活动性肝病(包括不能解释的持续性⾎清氨基转移酶升⾼)患者。
●Patients with a known hypernsitivity to any component of this product [e Adver
Reactions (6.1)].
对本药任⼀成分过敏者。
5 WARNINGS AND PRECAUTIONS 警告和注意事项
5.1 Risk of Hepatotoxicity 肝毒性风险
KYNAMRO can cau elevations in transaminas and hepatic steatosis, as described below. To what extent KYNAMRO-associated hepatic steatosis promotes the elevations in transaminas is unknown. There is concern that KYNAMRO could induce steatohepatitis, which can progress to cirrhosis over veral years. The clinical studies supporting the safety and efficacy of KYNAMRO in HoFH would have been unlikely to detect this adver outcome given their size and duration [e Clinical Studies (14)].
罗马语
本药可导致氨基转移酶升⾼和脂肪肝。尚不明确本药相关的脂肪肝促进氨基转移酶升⾼的程度。但担⼼本药可导致脂肪肝，并可在数年内进展为肝硬化。临床研究数据⽀持本药⽤于HoFH的安全性和有效性，但根据试验的规模和持续时间，不太可能检测到这些不良结果。
Elevation of Transaminas 氨基转移酶升⾼
KYNAMRO can cau increas in rum transaminas (alanine aminotransfera [ALT] and/or as
partate aminotransfera [AST]). In the clinical trial, 4 (12%) of the 34 subjects with HoFH treated with KYNAMRO compared to 0% of the 17 subjects treated with placebo had an elevation in ALT ≥ 3x ULN, and 3 (9%) of tho treated with KYNAMRO compared to 0% treated with placebo had at least one elevation in ALT ≥ 5x ULN.
本药可导致⾎清氨基转移酶(ALT和/或AST)升⾼。在本药的临床试验中，34名接受本药治疗HoFH的患者，有4名(12%)患者出现ALT≥3倍ULN，有3名(9%)患者出现ALT≥5倍ULN，⽽17名接受安慰剂的患者0%⼈出现。
panelistMeasure a full liver panel to include ALT, AST, total bilirubin, and alkaline phosphata before initiation of treatment with KYNAMRO [e Dosage and Administration (2.1)]. KYNAMRO is contraindicated in patients with moderate or vere hepatic impairment, or active liver dia, including unexplained persistent elevations of rum transaminas. If the baline liver-related
tests are abnormal, consider initiating KYNAMRO after an appropriate work-up and the baline abnormalities are explained or resolved. During the first year, conduct liver-related tests monthly (ALT and AST, at a minimum). After the first year, conduct the tests at least every 3 months. Discontinue KYNAMRO for persistent or clinically significant elevations [e Dosage and Administration (2.3)].
开始本药治疗前，应检测肝功能(包括ALT、AST、总胆红素、碱性磷酸酶)。本药禁⽤于中⾄重度肝损害、活动性肝病(包括不能解释的持续性⾎清氨基转移酶升⾼)患者。如肝功能相关试验的基线不正常，可考虑进⾏适当的诊断检查，基线异常的情况得到解释或缓解后，再开始⽤药。开始⽤药的第⼀年，每⽉检测肝功能(⾄少包括AST、ALT)。第⼀年后，⾄少每3个⽉检查⼀次。如出现持续或临床显著的升⾼，应停药。
If transamina elevations are accompanied by clinical symptoms of liver injury (e.g., naua, vomiting, abdominal pain, fever, jaundice, lethargy, flu-like symptoms), increas in bilirubin ≥2x ULN, or active liver dia, discontinue treatment with KYNAMRO and identify the probable cau.
如氨基转移酶升⾼并伴有肝损害的临床症状(如恶⼼、呕吐、腹痛、发热、黄疸、嗜睡、流感样症状)、胆红素≥2倍ULN或活动性肝病，应停⽤本药并调查以确定可能的原因。
Hepatic Steatosis 肝脏脂肪变性
KYNAMRO increas hepatic fat (steatosis) with or without concomitant increas in transaminas [e Adver Reactions (6.1)]. Hepatic steatosis is a risk factor for advanced liver dia, including steatohepatitis and cirrhosis. The long-term conquences of hepatic steatosis associated with KYNAMRO therapy are unknown. During the clinical trials in patients with heterozygous familial hype
rcholesterolemia (HeFH) and hyperlipidemia, the median absolute increa in hepatic fat was 10% after 26 weeks of treatment, from 0% at baline, measured by magnetic resonance imaging (MRI).
本药可增加肝脏脂肪(脂肪变性)，伴或不伴氨基转移酶升⾼。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。尚不明确与本药治疗相关的肝脏脂肪变性的长期结果。在本药治疗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%。
Alcohol may increa levels of hepatic fat and induce or exacerbate liver injury. It is recommended that patients taking KYNAMRO should consume no more than one alcoholic drink per day.
中国奥运代表团正式亮相
酒精可增加肝脏脂肪⽔平，并导致或使肝损伤恶化。建议接受本药治疗的患者，每⽇不应饮⽤超过⼀种酒精饮料。
Caution should be exercid when KYNAMRO is ud with other medications known to have potential for hepatotoxicity, for example isotretinoin, amiodarone, acetaminophen (>4 g/day for ≥3 days/week), methotrexate, tetracyclines, and tamoxifen. The effect of concomitant administration of KYNAMRO with other hepatotoxic medications is unknown. More frequent monitoring of
颜色英文liver-related tests may be warranted.
使⽤其他已知具有潜在肝毒性的药物(如异维A酸、胺碘酮、对⼄酰氨基酚(超过⼀⽇4g或⼀周内服药≥3⽇)、甲氨蝶呤、四环素和他莫昔芬)时，应慎⽤本药。尚不明确本药与其他肝毒性药物合⽤的影响。可能需要更频繁地检测肝脏相关试验。
Mipomern has not been studied concomitantly with other LDL-lowering agents that can also increa hepatic fat. Therefore, the combined u of such agents is not recommended.
尚未进⾏本药与其他降低LDL且增加肝脏脂肪的药物合⽤的研究。因此，不建议合⽤。
5.2 KYNAMRO REMS
Becau of the risk of hepatotoxicity, KYNAMRO is available only through a limited program under the REMS. Under the KYNAMRO REMS, only certified healthcare providers and pharmacies may prescribe and distribute KYNAMRO. Further information is available at
/doc/c5a49b966f1aff00bfd51e01.html or by telephone at 1-877-KYNAMRO (1-877596-2676).
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。根据KYNAMRO REMS，只有注册医师和药师能使⽤本药。
5.3 Injection Site Reactions 注射部位反应
Injection site reactions have been reported in 84% of patients receiving KYNAMRO therapy. The local reactions typically consist of one or more of the following: erythema, pain, tenderness, pruritus and local swelling. Injection site reactions do not occur with all injections but resulted in discontinuation of therapy in 5% of patients in pooled Pha 3 trials. [See Adver Reactions (6.1)] To minimize the potential for injection site reactions, proper technique for subcutaneous administration should be followed. [e Patient Counling Information (17)]
⽤药后有84%患者出现注射部位反应的报道。局部注射部位反应包括以下⼀种或多种典型症状：红斑、注射部位疼痛、压痛、瘙痒、局部肿胀。在临床试验3期，有5%患者因注射部位反应停药。为减轻注射部位反应的可能性，应遵从适当的⽪下注射技巧。
5.4 Flu-Like Symptoms 流感样症状
Flu-like symptoms have been reported in 30% of patients receiving KYNAMRO therapy and include
one or more of the following: influenza-like illness, pyrexia, chills, myalgia, arthralgia, malai or fatigue. Flu-like symptoms, which typically occur within 2 days after an injection, do not occur with all injections but resulted in discontinuation of therapy in 3% of patients in pooled Pha 3 trials. [See Adver Reactions (6.1)]
⽤药后有30%患者出现流感样症状的报道，流感样症状包括以下⼀种或多种症状：流感样疾病、发热、寒战、肌痛、关节痛、不适或疲乏。在临床试验3期，流感样症状主要在注射后2⽇内出现，有3%患者因流感样症状停药。
6 ADVERSE REACTIONS 不良反应
The following important adver reactions have been obrved and are discusd in detail in other ctions of the label:
下列观察到的重要不良反应已在本说明书其他章节讨论：
Risk of hepatotoxicity [e Warnings and Precautions (5.1)] 肝毒性风险
6.1 Clinical Trials 临床试验
Becau clinical trials are conducted under widely varying conditions, adver reaction rates obrved in clinical trials of a
