2007年5月3日,Supprelin-LA(醋酸组氨瑞林皮下植入剂)50mg在美国FDA批准上市,用于治疗儿童性早熟(CPP)。Supprelin-LA是一种一年期的皮下植入剂,12个月每天持续释放65μg促性腺激素释放激素类似物组氨瑞林,从而可以有效的阻碍垂体腺产生促性腺激素.
SUPPRELIN  LA（醋酸组氨瑞林[histrelin acetate]）皮下移植
最初美国批准：1991年
作用机理
SUPPRELIN LA是一个GnRH激动剂和连续给予时促性腺激素分泌的抑制剂。它提供大约每天65微克组氨瑞林醋酸。动物和人类的研究表明，以下的初始刺激阶段，组氨瑞林醋酸慢性，皮下给药脱敏垂体促性腺激素，这反过来导致在卵巢和睾丸类固醇减少的响应性。
在人类，的组氨瑞林醋酸导致在循环LH和FSH水平的初始增加，从而导致在性腺类固醇（睾酮和男性双氢，和雌酮和雌二醇在绝经前女性）的浓度的瞬时增加施用。
然而，组氨瑞林醋酸连续给药引起的GnRH受体的垂体促性腺激素的垂体和脱敏的可逆下调。这些抑制作用导致LH和FSH的水平降低。
适应症和用法
SUPPRELIN LA是促性腺激素释放激素（GnRH），与中枢性性早熟（CPP）患儿的治疗表明激动剂。
用法用量
SUPPRELIN LA的推荐剂量是每12个月一个植入物。所述植入物被插入皮下的上臂的内方面，并提供了组氨瑞林的连续释放12个月激素疗法。
剂型和规格
SUPPRELIN LA可作为50毫克醋酸组氨瑞林的皮下植入物超过12个月提供大约每天65微克组氨瑞林醋酸。
禁忌症
过敏史促性腺激素释放激素（GnRH）促性腺激素释放激素或类似物。
怀孕：怀孕期间使用时SUPPRELIN LA可引起胎儿危害。
警告和注意事项
最初的激动作用：雌二醇和/或睾酮的最初瞬间增加可能会造成暂时性的症状恶化。
不良反应
最常见的不良反应是植入位点反应（51.1％），包括与植入物的插入或移除的并发症。
可能会出现与内源性性激素分泌抑制不良事件。
特殊人群中使用
不建议在孩子不到2岁的用途SUPPRELIN LA的。
包装规格/储存与处理
SUPPRELIN LA（NDC 67979-002-01），其中包含2内纸箱瓦楞装运箱提供：一个小的为包含SUPPRELIN LA植入小瓶，它随聚苯乙烯冷却器内冷包必须冷藏到来，一个较大的包括植入工具包，不能冷藏，使用SUPPRELIN LA的插入或拔出时后。
该SUPPRELIN LA植入物中含有50毫克的醋酸组氨瑞林的。
该SUPPRELIN LA植入纸箱包含冷藏运输和含有琥珀塑料袋一个小纸盒感冒包。袋内是玻璃小瓶用聚四氟乙烯涂覆的塞子和铝密封层，含在2mL无菌1.8％氯化钠溶液的植入物。 （注：3.5毫升小瓶未完全充满盐水）。
一旦收到，含冷藏直到插入一天琥珀塑料袋和玻璃小瓶（里面植入）的小纸盒。植入物小瓶不应该被打开，直到刚刚插入的时间之前。
直到时提供的到期日冷藏保存，在密封的小瓶，袋，和纸箱，在2-8°C（36-46°F）SUPPRELIN LA是稳定的。游览允许25°C（77°F）7天。不要冻结。避光
INDICATION
SUPPRELIN® LA (histrelin acetate) subcutaneous implant is indicated for the treatment of children with central precocious puberty (CPP)
Children with CPP (neurogenic or idiopathic) have an early onset of secondary sexual characteristics (earlier than 8 years of age in females and 9 years of age in males). They also show a significantly advanced bone age that can result in diminished adult height attainment
Prior to initiation of treatment a clinical diagnosis of CPP should be confirmed by measurement of blood concentrations of total sex steroids, luteinizing hormone (LH) and follicle stimulating hormone (FSH) following stimulation with a GnRH analog, and assessment of bone age versus chronological age. Baseline eva luations should include height and weight measurements, diagnostic imaging of the brain (to rule out intracranial tumor), pelvic/testicular/adrenal ultrasound (to rule out steroid secreting tumors), human chorionic gonadotropin levels (to rule out a chorionic gonadotropin secreting tumor), and adrenal steroids to exclude congenital adrenal hyperplasia
IMPORTANT SAFETY INFORMATION about SUPPRELIN® LA
SUPPRELIN® LA is contraindicated in patients who are hypersensitive to gonadotropin releasing hormone (GnRH) or GnRH agonist analogs and in females who are or may become pregnant while receiving the drug. SUPPRELIN® LA is pregnancy Category X. SUPPRELIN® LA may cause fetal harm or spontaneous abortion when administered to pregnant patients. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus
SUPPRELIN® LA, like other GnRH agonists, initially causes a transient increase in serum concentrations of estradiol in females and testosterone in both sexes during the first week of treatment, with worsening or onset of new symptoms during this period. Within 4 weeks of therapy, gonadal steroid suppression occurs and manifestations of puberty decrease
Implant insertion and removal is a surgical procedure and should utilize aseptic technique. Careful adherence to the recommended insertion and removal procedures is recommended to avoid potential complications. Proper surgical technique is critical in minimizing adverse events related to the insertion and the removal of the histrelin implant. On occasion, localizing and/or removal of implant products have been difficult and imaging techniques were used including ultrasound, CT, or MRI (this implant is not radiopaque). In some cases the implant broke during removal and multiple pieces were recovered. Rare events of spontaneous extrusion have been observed in clinical trials. During SUPPRELIN® LA treatment, patients should be eva luated for evidence of clinical and biochemical suppression of CPP manifestation
LH, FSH and estradiol or testosterone should be monitored at 1 month post implantation then every 6 months. Every 6-12 months, height and bone age should be assessed
In clinical trials, the most common adverse reactions involved the implant site and included discomfort, bruising, soreness, pain, tingling, itching, erythema, and implant area protrusion and swelling
Seizures (Nervous system disorders) have been identified during post-approval use of SUPPRELIN® LA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure
The safety and effectiveness in pediatric patients under the age of 2 years has not been established. The use of SUPPRELIN®  LA in children under 2 years is not recommended
Please see full Prescribing Information for SUPPRELIN® LA.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d8fb000e-3cc9-4803-b71d-2cc597661977