近日，美国食品和药物管理局（FDA）批准DUOPA（carbidopa and levodopa）肠内悬液用于治疗人体运动波动 伴有晚期帕金森病。DUOPA使用小型便携式输液泵进行给药，该输液泵通过程序放置的管将卡比多巴和左旋多巴直接连续16小时输送到小肠。
DUOPA是一种新的方法，用于治疗晚期帕金森病患者的运动波动。carbidopa and levodopa被广泛认为是治疗疾病运动波动的有效方法.5 DUOPA经FDA审查并批准为使用CADD Legacy 1400泵的组合产品。
批准日期：2015年1月25日 公司：AbbVie Inc
DUOPA（卡比多巴和左旋多巴[carbidopa and levodopa]）肠内悬浮液
最初的美国批准：1975年
最近的重大变化
警告和注意事项，胃肠道和
与胃肠道程序有关的风险：9/2016
作用机制
卡比多巴
当左旋多巴口服给药时，它在脑外组织中迅速脱羧成多巴胺，因此只有一小部分给定剂量不变地运输到中枢神经系统。卡比多巴抑制外周左旋多巴的脱羧，使更多的左旋多巴可用于递送至大脑。
左旋多巴
左旋多巴是多巴胺的代谢前体，穿过血脑屏障，可能在大脑中转化为多巴胺。这被认为是左旋多巴治疗帕金森病症状的机制。
适应症和用法
DUOPA是卡比多巴（一种芳香族氨基酸脱羧抑制剂）和左旋多巴（一种芳香族氨基酸）的组合，用于治疗晚期帕金森病患者的运动波动。
剂量和给药
DUOPA的最大推荐日剂量是在16小时内给予2000mg左旋多巴（即每天一个盒）。
在启动DUOPA之前，将患者从所有形式的左旋多巴转换为口服速释卡比多巴 - 左旋多巴片剂（1：4比例）。
根据患者的临床反应滴定总日剂量。
通过带有空肠管（PEG-J）的经皮内窥镜胃造口术和CADD®-Legacy 1400便携式输液泵将DUOPA管理到空肠中。
剂量形式和强度
肠内悬浮液：每mL含4.63mg卡比多巴和20mg左旋多巴。
禁忌症
DUOPA禁用于服用非选择性单胺氧化酶（MAO）抑制剂的患者。
警告和注意事项
与胃肠道手术相关的并发症可能导致严重后果，例如需要手术或死亡。
在日常生活活动中可能会入睡。
监测患者的体位性低血压，特别是在开始DUOPA或增加剂量后。
幻觉/精神病/混乱：可能对左旋多巴的剂量减少有反应。
脉冲控制障碍：考虑减少剂量或停止DUOPA
监测患者的抑郁和自杀倾向。
避免突然停药或快速减少剂量，以减少出现退缩性高热和混淆的风险。
可能导致或加剧运动障碍：考虑减少剂量。
监测患者周围神经病变的体征和症状。
不良反应
DUOPA最常见的不良反应（DUOPA发生率比口服卡比多巴 - 左旋多巴发病率至少高7％）是：器械插入并发症，恶心，抑郁，外周性水肿，高血压，上呼吸道感染，口咽疼痛，肺不张和切口部位红斑。
要报告可疑的不良反应，请致电1-800-633-9110联系AbbVie Inc.或致电1-800-FDA-1088或WWW.FDA.GOV/MEDWATCH联系FDA。
药物相互作用
选择性MAO-B抑制剂：可能引起直立性低血压。
抗高血压药：可引起症状性体位性低血压。可能需要调整抗高血压药物的剂量。
多巴胺D2受体拮抗剂，异烟肼，铁盐和高蛋白饮食可降低DUOPA的有效性。
用于特定人群
怀孕：根据动物数据，可能会造成胎儿伤害。
包装提供/存储和处理
提供
一次性盒含有4.63mg卡比多巴（作为5mg一水合物）和20mg左旋多巴/mL肠内悬浮液。每个盒包含约100mL的悬浮液。
纸箱7个DUOPA磁带：NDC 0074-3012-07
存储和处理
储存在-20oC（-4oF）的冰箱中。在分配之前，在2oC至8oC（36oF至46oF）的冰箱中解冻。应保护盒式磁带免受光照并在使用前保存在纸盒中。
解冻药房的说明
根据纸箱放入冰箱解冻的时间，分配12周的“使用期限”。
在分配之前将DUOPA完全解冻在冰箱中。
为了确保DUOPA的可控解冻，将包含七个单独盒的纸箱从运输箱中取出并将纸箱彼此分开。
当纸箱从运输箱中取出时，解冻可能需要长达96小时。
一旦产品解冻，单个纸箱可以在冰箱内以更紧密的配置包装。
DUOPA(carbidopa and levodopa) enteral suspension
Initial U.S. Approval: 1975
Indication and Important Safety Information
DUOPA enteral suspension is indicated for the treatment of motor fluctuations in patients with advanced Parkinson’s disease.
DUOPA is contraindicated in patients who are currently taking or have taken (within 2 weeks) a nonselective monoamine oxidase (MAO) inhibitor, as concurrent use can cause hypertension.
A Percutaneous Endoscopic Gastrostomy with Jejunal Extension (PEG-J) is contraindicated with lack of transillumination/positive needle aspiration test; intestinal obstruction; sepsis; peritonitis; serious coagulation disorders; ascites; and neoplastic, inflammatory, and infiltrative diseases of the gastric and abdominal walls.
Because DUOPA is administered using a PEG-J or naso-jejunal tube, gastrointestinal complications can occur, including bezoar; ileus; implant site erosion/ulcer; intestinal hemorrhage, ischemia, obstruction, or perforation; intussusception; pancreatitis; peritonitis; pneumoperitoneum; and wound infection, any of which may require surgery or be fatal.
Instruct patients to immediately report abdominal pain, prolonged constipation, nausea, vomiting, fever, or melanotic stool.
Patients treated with levodopa (a component of DUOPA) have reported falling asleep while engaged in activities of daily living, including the operation of motor vehicles, which sometimes resulted in accidents. Although many of these patients reported somnolence while on levodopa, some perceived that they had no warning signs (sleep attack), such as excessive drowsiness, and believed they were alert immediately prior to the event.
For this reason, prescribers should reassess patients for drowsiness or sleepiness in DUOPA-treated patients, especially since some of the events occur well after the start of treatment.
Advise patients about the potential to develop drowsiness with DUOPA and ask about factors that may increase risk of somnolence. Consider discontinuing DUOPA in patients who report significant daytime sleepiness or episodes of falling asleep during activities that require active participation.
For these patients, if a decision is made to continue DUOPA, advise them to avoid driving and other potentially dangerous activities that might result in harm if the patients become somnolent.
Monitor patients for orthostatic hypotension, especially after starting DUOPA or increasing the dose.
There is an increased risk for hallucinations, psychosis, and confusion in patients taking DUOPA. Hallucinations associated with levodopa may present shortly after the initiation of therapy and may be responsive to dose reduction of levodopa. Patients with a major psychotic disorder should not be treated with DUOPA.
Patients may experience intense urges while on DUOPA. Because patients may not recognize these behaviors as abnormal, it is important for prescribers to ask patients or their caregivers specifically about the development of new or increased gambling urges, sexual urges, uncontrolled spending, binge or compulsive eating, or other urges while on DUOPA. Consider reducing the dose or discontinuing DUOPA if a patient develops such urges.
Depression has been reported in patients treated with DUOPA. Monitor patients for depression and concomitant suicidal tendencies.
Withdrawal-emergent hyperpyrexia and confusion, a symptom complex that resembles neuroleptic malignant syndrome (characterized by elevated temperature, muscular rigidity, altered consciousness, and autonomic instability), with no other obvious etiology, has been reported in association with rapid dose reduction, withdrawal, or change in dopaminergic therapy. Avoid sudden discontinuation or rapid dose reduction of DUOPA.
DUOPA may cause or exacerbate dyskinesias, which may require a dose reduction of DUOPA or other Parkinson's disease medications.
Generalized polyneuropathy has been reported in patients receiving DUOPA. Assess patients for the signs and symptoms of peripheral neuropathy before and periodically after starting DUOPA, especially patients with pre-existing neuropathy, patients taking medications, or those who have medical conditions associated with neuropathy.
Myocardial infarction and arrhythmia were reported in patients taking carbidopa-levodopa. Ask patients about symptoms of ischemic heart disease and arrhythmia, especially those with a history of myocardial infarction or cardiac arrhythmias.
Parkinson's disease patients have a higher risk of developing melanoma than the general population and should be monitored periodically for melanoma.
DUOPA may increase the risk for elevated blood urea nitrogen (BUN) and creatine phosphokinase (CPK). Patients taking levodopa may have increased levels of catecholamines and their metabolites in plasma and urine, giving false positive results that suggest the diagnosis of pheochromocytoma.
Monitor patients with glaucoma after starting DUOPA, as it may cause increased intraocular pressure.
Drug Interactions: Monitor patients taking selective MAO-B inhibitors and carbidopa-levodopa for orthostatic hypotension. Concurrent administration with antihypertensives may result in postural hypotension, necessitating a dose reduction of the antihypertensive.
Co-administration with dopamine D2 antagonists, isoniazid, or iron salts may reduce effectiveness of DUOPA.
The most common adverse events for DUOPA, with an incidence at least 7% greater than oral carbidopa-levodopa immediate release (CLIR), were (DUOPA vs. CLIR): complication of device insertion (57% vs 44%), nausea (30% vs 21%), depression (11% vs 3%), peripheral edema (8% vs 0%), hypertension (8% vs 0%), upper respiratory tract infection (8% vs 0%), oropharyngeal pain (8% vs 0%), atelectasis (8% vs 0%), and incision site erythema (19% vs 12%).
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7066d371-dc6a-0d6f-7bed-e5dd4ee912da