【中文品名】美卡舍明
【药效类别】抗糖尿病药，抗侏儒症药
【通用药名】MECASERMIN
【别　　名】FK-780, IGF-1, Somazon, Somatomedin-1, Somatomedin-C
【化学名称】 Insulin-like growth factor I
【CA登记号】[67763-96-6]
【结 构 式】

【分 子 式】CHNOPS·
【分 子 量】
【收录药典】
【开发单位】藤泽
【首次上市】1995年，日本
【性　　状】
【用　　途】
一种重组Somatomedin-1，用于胰岛素抗性糖尿病和抗生长激素的侏儒症。还可用于骨疾病，如骨质疏松症、骨折、类风湿性关节炎和治疗溃疡、烧伤和创伤。

INCRELEX - mecasermin injection, solution
Tercica, Inc.
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INCRELEX® (mecasermin [rDNA origin] injection]
Initial U.S. Approval: 2005

RECENT MAJOR CHANGES
Contraindications, Known Hypersensitivity

Warnings and Precautions, Hypersensitivity and Allergic Reactions, including Anaphylaxis 
INDICATIONS AND USAGE
INCRELEX® (mecasermin [rDNA origin] injection) is indicated for:

the treatment of growth failure in children with severe primary IGF-1 deficiency or with growth hormone (GH) gene deletion who have developed neutralizing antibodies to GH.
Limitations of use: INCRELEX® is not a substitute to GH for approved GH indications.
DOSAGE AND ADMINISTRATION
INCRELEX® should be administered subcutaneously.
Injection sites should be rotated to avoid lipohypertrophy.
Recommended starting dose: 0.04 to 0.08 mg/kg (40 to 80 micrograms/kg) twice daily. If well-tolerated for at least one week, the dose may be increased by 0.04 mg/kg per dose, to the maximum dose of 0.12 mg/kg given twice daily.
DOSAGE FORMS AND STRENGTHS
INCRELEX® is a sterile solution supplied in a multiple dose glass vial at a concentration of 10 mg per mL (40 mg per vial).
CONTRAINDICATIONS
Active or Suspected Neoplasia
Known Hypersensitivity to mecasermin
Intravenous Administration
Closed Epiphyses 
WARNINGS AND PRECAUTIONS
INCRELEX® should be administered shortly before or after a meal or snack, because it has insulin-like hypoglycemic effects.
Hypersensitivity and Allergic Reactions, including Anaphylaxis: A low number of cases indicative of anaphylaxis requiring hospitalization have been reported. Parents and patients should be informed that such reactions are possible and that if a systemic allergic reaction occurs, treatment should be interrupted and prompt medical attention should be sought.
Intracranial Hypertension: Funduscopic examination is recommended at the initiation and periodically during the course of INCRELEX® therapy.
Lymphoid Tissue Hypertrophy (tonsillar/adenoidal hypertrophy): Patients should have periodic examinations to rule out potential complications and receive appropriate treatment if necessary.
Slipped Capital Femoral Epiphysis (SCFE): Evaluate any child with onset of a limp or hip/knee pain for possible SCFE.
Progression of Scoliosis: Monitor any child with scoliosis for progression of the spine curve.
ADVERSE REACTIONS
Common INCRELEX®-related adverse reactions in clinical trials include: hypoglycemia , local and systemic hypersensitivity , tonsillar hypertrophy

To report SUSPECTED ADVERSE REACTIONS, contact Tercica at 1-866-837-2422 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
USE IN SPECIFIC POPULATIONS
Pregnancy: Based on animal data, INCRELEX® may cause fetal harm.
Pediatric Use: Safety and effectiveness has not been established in children less than 2 years of age.

See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling 

Revised: 02/2011 

Increlex® is the only FDA-approved treatment for severe Primary IGFD
Recognition of IGF-1 and IGF-1 replacement therapy continues to grow. Increased understanding of the role of IGF-1 in short stature and severe Primary IGFD has led to long-term clinical trials and proven effectiveness of the only FDA-approved therapy for the treatment of severe Primary IGFD, as defined by:1

Height standard deviation score ≤ -3.0 and
Basal IGF-1 standard deviation score ≤ -3.0 and
Normal or elevated growth hormone (GH)
Consider Increlex when growth hormone insensitivity is suspected. Increlex is also approved for patients with GH gene deletion who have developed neutralizing antibodies to GH.1

Increlex has an identical sequence to that of endogenous human IGF-1. Increlex is a well tolerated and effective treatment for patients diagnosed with severe Primary IGFD.
Indication and Important Safety Information 1
INCRELEX® (mecasermin [rDNA origin] injection) is indicated for the long-term treatment of growth failure in children with severe Primary IGF-1 deficiency (Primary IGFD) or with growth hormone (GH) gene deletion who have developed neutralizing antibodies to GH. Severe Primary IGFD is defined by:

height standard deviation score ≤ -3.0 and
basal IGF-1 standard deviation score ≤ -3.0 and
normal or elevated growth hormone (GH).
Severe Primary IGFD includes patients with mutations in the GH receptor (GHR), post-GHR signaling pathway, and IGF-1 gene defects; they are not GH deficient, and therefore, they cannot be expected to respond adequately to exogenous GH treatment.

INCRELEX is not intended for use in subjects with secondary forms of IGF-1 deficiency, such as GH deficiency, malnutrition, hypothyroidism, or chronic treatment with pharmacologic doses of anti-inflammatory steroids. Thyroid and nutritional deficiencies should be corrected before initiating INCRELEX treatment.

INCRELEX is not a substitute for GH treatment.

INCRELEX should not be used for growth promotion in patients with closed epiphyses. INCRELEX is contraindicated in the presence of active or suspected neoplasia, and therapy should be discontinued if evidence of neoplasia develops. Intravenous administration of INCRELEX is contraindicated. INCRELEX should not be used by patients who are allergic to mecasermin (IGF-1) or any of the inactive ingredients in INCRELEX.

INCRELEX contains benzyl alcohol as a preservative, which has been associated with neurologic toxicity in neonates.

INCRELEX has not been studied in patients under 2 years old.

Slipped capital femoral epiphysis and progression of scoliosis can occur in patients who experience rapid growth.

Local or systemic allergic reactions may occur.

In clinical studies of 71 subjects with severe Primary IGFD treated for a mean duration of 3.9 years and representing 274 subject-years, no subjects withdrew from any clinical study because of adverse events.

Hypoglycemia was reported by 30 subjects (42%) at least once during their course of therapy. Of the 30 subjects reporting hypoglycemia, 14 (47%) had a history of hypoglycemia prior to treatment. Most cases were mild or moderate in severity. Five subjects had severe hypoglycemia (requiring assistance and treatment) on one or more occasion, and four subjects experienced hypoglycemic seizures/loss of consciousness on one or more occasion. The frequency of hypoglycemia was highest in the first month of treatment, and episodes were more frequent in younger children. Hypoglycemia was generally avoided when a meal or snack was consumed either shortly before or shortly after administration.

Tonsillar hypertrophy was noted in 11 subjects (15%) in the first 1 to 2 years of therapy with lesser tonsillar growth in subsequent years.

Intracranial hypertension occurred in three subjects. In two subjects, the events resolved without interruption of Increlex treatment. Increlex treatment was discontinued in the third subject and resumed later at a lower dose without recurrence.

【药物名称】
中文通用名称：美卡舍明
英文通用名称：Mecasermin
其他名称：基因重组胰岛素生长因子-1、Increlex、Rdnaigf-1、Somatomedin-1、Somatomedin-C、Somazon。
【临床应用】
用于重度原发性胰岛素样生长因子1缺乏(IGFD)的儿童(国外资料)。
【药理】
1.药效学  本药是重组人胰岛素样生长因子1(IGF-1)。内源性IGF-1为正常生长和大脑发育所必需，有介导生长激素的合成代谢、促进生长及影响葡萄糖、脂肪和氨基酸摄取以便使代谢支持生长的作用。此外，本药还可增加胰岛素的敏感性，并有胰岛素的某些作用(有6%-11%的降葡萄糖作用)。
2.药动学  本药在健康受试者中的生物利用度接近100%。皮下注射单剂0.12mg/kg后，平均达峰时间是2小时，平均峰浓度是234ng/ml，平均曲线下面积(AUC)是2932(ng•h)/ml。药物吸收后与蛋白高度结合，在血浆中形成胰岛素样生长因子结合蛋白(IGFBP)，80%以上的IGF-1结合形成IGFBP-3及一种酸不稳定性蛋白亚单位，重度原发性IGFD患者形成的IGFBP-3较健康受试者明显减少，增加了IGF-1的清除。分布容积为0.257L/kg，在肝和肾代谢，总体清除率为0.04L/(kg•h)，平均半衰期是5.8小时。
【注意事项】
1.禁忌症  (1)对本药过敏者。(2)骨骺愈合者。(3)已有或怀疑有肿瘤者。(以上均选自国外资料)
2.慎用  尚不明确。
3.药物对妊娠的影响  动物研究已表明本药对胎仔有不良效应(致畸、死胎或其他)。尚缺乏孕妇用药的安全性数据，使用时应权衡利弊。美国食品药品管理局(FDA)对本药的妊娠安全性分级为C级。
4.药物对哺乳的影响  尚不明确哺乳期用药对乳儿的危害，使用时应权衡利弊。
5.用药前后及用药时应当检查或监测
(1)治疗开始及治疗过程中应坚持眼底镜检查。
(2)定期检查以监测是否出现扁桃及淋巴结肥大。
【不良反应】
[国外不良反应参考]
1.心血管系统  常见颜面浮肿、外周水肿，可见低血压，偶见心动过速。少数患者出现无症状性心脏肥大或心脏瓣膜病变，但与本药的因果关系尚未确定。
2.代谢/内分泌系统  可见低血糖(42%)、体重增加；较常见腮腺肿大；罕见男子乳腺发育。
3.肌肉骨骼系统  常见下颚痛；较常见关节痛、肌痛；快速生长的患者可能出现脊柱侧凸畸形、股骨骨骺滑脱。
4.泌尿生殖系统  据报道，用药后血清肌酸酐或肌酐清除率无变化。
5.免疫系统  可见抗IGF-1抗体形成(61%)、扁桃腺肥大(15%)。未见变态反应的报道，但任何外源性蛋白类均可能发生局部或全身变态反应，如发生，应暂停治疗，并立即处置。
6.神经系统  可见头晕(≥5%)、头痛(≥5%)、颅内压升高(4.2%)、癫痫发作(≥5%)；少见失眠。新生儿可能出现神经毒性。
7.肝脏  可见天门冬氨酸氨基转移酶和乳酸脱氢酶轻度升高。
8.胃肠道  可见呕吐(≥5%)、恶心(不常见)。
9.皮肤  较常见发汗，可见皮疹、潮红或苍白、头发生长、脸部软组织增厚、注射部位疼痛或反应(脂质增生和瘀伤)。
10.眼  可见视网膜病变，但与本药的因果关系尚未确定。
【药物相互作用】
尚不明确。
【给药说明】
1.本药禁忌静脉给予。
2.应在进食前后短时间内给药。
3.用药后不宜驾驶、操作机械或从事高危活动；由于低血糖效应，给药后2-3小时内应限制活动。
【用法与用量】
[国外用法用量参考]
儿童
•常规剂量
•皮下注射  初始剂量为一次0.04-0.08mg/kg，一日2次；维持剂量可每剂增加0.04mg/kg，最大剂量为一次0.12mg/kg，一日2次。
【制剂与规格】
美卡舍明注射液  4ml:40mg。
贮法：药瓶开启前后均应贮于2-8℃冰箱内，避光，不可冷冻。

厂家Tercica Europe Limited

法国；规格：INCRELEX 10 mg/ml Solution injectable Bo te de 1 Flacon de 4 ml
西班牙是IPSEN 厂家：INCRELEX Sol. iny. 10 mg/ml env. con 1 vial de 4 ml