近日，美国食品和药物管理局FDA在其专有的SynchroMed II植入药物输注系统，非常久远一个新的导管，以与联合治疗的Remodulin（treprostinil）注射，配方为肺动脉高压（PAH）静脉内治疗中。
批准日期：2002年5月22日 公司：United Therapeutics
REMODULIN（曲前列环素[treprostinil]）注射液，用于皮下或静脉注射
美国最初批准：2002年5月
最近的重大变化
剂量和用法：07/2018
警告和注意事项：07/2018
作用机制
曲前列环素的主要药理作用是肺和全身动脉血管床的直接血管舒张，以及血小板聚集的抑制。
适应症和用法
Remodulin是一种前列环素血管扩张剂，适用于：
治疗肺动脉高压（PAH; WHO组1）以减少与运动相关的症状。确定有效性的研究包括NYHA II-IV级功能症状和特发性或遗传性PAH病因（58％），先天性全肺 - 肺分流相关PAH（23％）或结缔组织病相关PAH（19％） ）。
需要从依前列醇过渡的患者，以降低临床恶化的速度。在过渡之前，应仔细考虑每种药物的风险和益处。
剂量和给药
PAH WHO第1组适用于NYHA II-IV级症状的患者：
新型前列环素输注治疗患者的初始剂量：1.25ng/kg/min;根据临床反应增加（治疗前4周每周增量为1.25ng/kg/min，之后每周增加2.5ng/kg/min）。避免突然停止。
轻度至中度肝功能不全：将初始剂量降至0.625ng/kg/min。
严重肝功能不全：未进行任何研究。
从依前列醇过渡：
基于对反应的持续观察，随着依前列醇剂量减少，逐渐增加调节剂量。
管理：
连续皮下输注是优选的模式。如果不允许皮下输注，则使用静脉内（IV）输注。
剂量形式和强度
在含有20,50,100或200mg曲前列环素（1,2.5,5或10mg/mL）的20mL小瓶中提供Remodulin。
禁忌症
没有
警告和注意事项
使用带有留置中心静脉导管的外部输液泵进行的慢性静脉输注与血流感染（BSI）和败血症的风险相关，这可能是致命的。
不要突然降低剂量或撤回剂量。
调节素可引起症状性低血压。
Remodulin抑制血小板聚集并增加出血风险。
不良反应
在使用Remodulin的临床研究中报告了最常见的不良反应（发生率> 3％）：皮下输注部位疼痛和反应，头痛，腹泻，恶心，下颌疼痛，血管扩张，水肿和低血压。
包装提供/存储和处理
Remodulin以20mL多剂量小瓶的形式提供，作为注射用水中的无菌溶液，单独包装在纸箱中。未开瓶的Remodulin在25°C（77°F）温度下保存至指定日期，允许偏移温度为2-30°C（36-86°F）。在最初引入小瓶后，应使用一小瓶Remodulin不超过30天。
Remodulin Injection提供如下：
Remodulin          浓度         NDC
20毫克/20毫升  1毫克/毫升   66302-101-01
50毫克/20毫升  2.5毫克/毫升 66302-102-01
100毫克/20毫升 5毫克/毫升   66302-105-01
200毫克/20毫升 10毫克/毫升  66302-110-01
用于Remodulin的无菌稀释剂单独提供：
50毫升小瓶，纸箱1（NDC 66302-150-50）
完整说明资料附件：
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6c80bb38-e8db-4138-9f0d-dbbf9c673185
Remodulin(treprostinil) Injection
Indication
Remodulin is a prostacyclin vasodilator indicated for the treatment of pulmonary arterial hypertension (PAH; WHO Group 1) to diminish symptoms associated with exercise. Studies establishing effectiveness included patients with NYHA Functional Class II-IV symptoms and etiologies of idiopathic or heritable PAH (58%), PAH associated with congenital systemic-to-pulmonary shunts (23%), or PAH associated with connective tissue diseases (19%).
In patients with PAH requiring transition from epoprostenol, Remodulin is indicated to diminish the rate of clinical deterioration. Consider the risks and benefits of each drug prior to transition.
Important Safety Information for Remodulin
Warnings and Precautions
Chronic intravenous (IV) infusions of Remodulin delivered using an external infusion pump with an indwelling central venous catheter are associated with the risk of blood stream infections (BSI) and sepsis, which may be fatal. Therefore, continuous subcutaneous (SC) infusion is the preferred mode of administration.
Avoid abrupt withdrawal or sudden large reductions in dosage of Remodulin, which may result in worsening of PAH symptoms.
Titrate slowly in patients with hepatic or renal insufficiency, because such patients will likely be exposed to greater systemic concentrations relative to patients with normal hepatic or renal function.
Remodulin is a pulmonary and systemic vasodilator. In patients with low systemic arterial pressure, treatment with Remodulin may produce symptomatic hypotension.
Remodulin inhibits platelet aggregation and increases the risk of bleeding.
Adverse Reactions
In clinical studies of SC Remodulin infusion, the most common adverse events reported were infusion site pain and infusion site reaction (redness, swelling, and rash). These symptoms were sometimes severe and sometimes required treatment with narcotics or discontinuation of Remodulin. The IV infusion of Remodulin with an external infusion pump has been associated with a risk of blood stream infections, arm swelling, paresthesias, hematoma, and pain. Other common adverse events (≥3% more than placebo) seen with either SC or IV Remodulin were headache (27% vs. 23%), diarrhea (25% vs. 16%), nausea (22% vs. 18%), rash (14% vs. 11%) jaw pain (13% vs. 5%), vasodilatation (11% vs. 5%), edema (9% vs. 3%), and hypotension (4% vs. 2%).
Drug Interactions
Remodulin dosage adjustment may be necessary if inhibitors or inducers of CYP2C8 are added or withdrawn.
Specific Populations
In patients with mild or moderate hepatic insufficiency, decrease the initial dose of Remodulin to 0.625 ng/kg/min of ideal body weight, and monitor closely. Remodulin has not been studied in patients with severe hepatic insufficiency.
Safety and effectiveness of Remodulin in pediatric patients have not been established.
It is unknown if geriatric patients respond differently than younger patients. Caution should be used when selecting a dose for geriatric patients.
There are no adequate and well-controlled studies with Remodulin in pregnant women. It is not known whether treprostinil is excreted in human milk or if it affects the breastfed infant or milk production.