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作者：Yael Waknine  
出處：WebMD醫學新聞

　　February 23, 2010 — 美國食品藥物管理局(FDA)核准一種新的每天服用一次的pramipexole dihydrochloride(商品名Mirapex ER錠劑，Boehringer Ingelheim Pharmaceuticals製藥公司)用於治療早期自發性巴金森氏症的徵兆與症狀。
　　
　　根據該公司的新聞稿，使用每天服用一次的延長釋出劑型，治療順從性優於服用每天三次的立即釋放劑型pramipexole錠劑。
　　
　　南佛羅里達大學醫學院巴金森氏症與動作異常中心主任、神經科教授Robert Hauser醫師表示，Mirapex ER用於早期巴金森氏症，是此一疾病治療之正向發展，這個新的、每天服用一次的治療，具有更方便的給藥時間，讓巴金森氏症患者可以更彈性地安排日常生活，一般而言，病患會因為便利性而偏好每天一次的處方。
　　
　　FDA的核准是根據一個18週、雙盲、多中心臨床試驗的資料(n > 400人)，結果顯示，相較於安慰劑，延長釋出劑型pramipexole之治療顯著改善了「統一巴金森氏症級別範圍(Unified Parkinson's Disease Rating Scale[UPDRS])」量表II 與量表 III相對於開始時的平均分數，且治療效果與立即釋放錠劑所達到的相當。
　　
　　UPDRS分數被用來追蹤巴金森氏症相關的失能與功能不佳的縱向病程；UPDRS量表II和量表III分別與日常生活活動和動作症狀有關。
　　
　　另一篇研究(n = 104人)的結果顯示，85%的早期巴金森氏症患者可以成功地立即從每天三次的pramipexole換成每天一次的延長釋出劑型pramipexole。前述成功轉換的定義為，UPDRS量表II和量表III分數惡化低於15%，且沒有因為停用其他兩次藥物的相關副作用，有一些案例則需要劑量調整。
　　
　　兩篇研究的安全性分析發現，每天一次的pramipexole其安全性與耐受性資料相似於立即釋放劑型，最常報告的副作用包括噁心、頭暈、睏倦、難以入睡、虛弱和便秘。
　　
　　FDA警告表示，接受pramipexole治療的病患一般都會發生睏倦；應提醒病患，從事駕車等日常生活活動時，應注意睏倦想睡的相關風險，也可能發生幻覺，特別是年長病患。
　　
　　有些接受pramipexole的病患發生強烈的賭博、性交與使用其他藥物的慾望，且無法控制這些慾望，雖然這與該藥物的因果關係尚未被確定，如果發生這類事件，建議減少劑量或者停止治療。
　　
　　病患可能也會發生站立型低血壓、可能伴隨有暈眩、噁心、昏倒/眼前發黑、盜汗等症狀，因為低血壓比較會在初次治療時發生，應提醒病患，在這段期間須避免在坐或躺時猛然起身。


FDA Approves Once-Daily Pramipexole for Early Parkinson's Disease

By Yael Waknine
Medscape Medical News

February 23, 2010 — The US Food and Drug Administration (FDA) has approved a new once-daily formulation of pramipexole dihydrochloride (Mirapex ER tablets, Boehringer Ingelheim Pharmaceuticals, Inc) for treating signs and symptoms of early idiopathic Parkinson's disease.

According to a company news release, use of the once-daily extended-release formulation rather than thrice-daily immediate-release pramipexole tablets may improve therapeutic compliance.

"Mirapex ER for early Parkinson's disease is a positive development in the treatment of this disease. This new, once-daily treatment has a more convenient dosing schedule, offering greater flexibility as someone with early Parkinson's disease plans his or her day," said Robert Hauser, MD, professor of neurology and director, Parkinson's Disease Movement Disorders Center, at the University of South Florida College of Medicine, Tampa. "In general, patients often prefer once-daily dosing to a more frequent regimen because of convenience."

FDA approval was based primarily on data from an 18-week, double-blind, multicenter clinical trial (n > 400) showing that extended-release pramipexole therapy significantly improved mean Unified Parkinson's Disease Rating Scale (UPDRS) II + III scores from baseline relative to placebo, with benefits comparable to that achieved with immediate-release tablets.

UPDRS scores are used to follow the longitudinal course of Parkinson's disease–related disability and impairment; the UPDRS parts II and III relate to activities of daily living and motor symptoms, respectively.

Findings from a second study (n = 104) demonstrated that 85% of patients with early Parkinson's disease were able to successfully switch overnight from thrice-daily pramipexole to the once-daily extended-release formulation. Success was defined as a 15% or less worsening of UPDRS II + III scores and a lack of adverse events leading to discontinuation of therapy. Dose adjustments were required in some cases.

A safety analysis of both studies revealed that the safety and tolerability profile of once-daily pramipexole was similar to that of the immediate-release formulation. Adverse events most commonly reported included nausea, dizziness, sleepiness, difficulty falling asleep, weakness, and constipation.

The FDA warns that somnolence is a common occurrence in patients receiving pramipexole therapy; patients should be advised regarding the risk of falling asleep while engaged in activities of daily living, including the operation of motor vehicles. Hallucinations may also occur, particularly in elderly patients.

Some patients receiving pramipexole have experienced intense gambling, sexual, and other urges, combined with an inability to control these urges. Although a causal role for the drug has not been established, dose reductions or discontinuation of therapy should be considered if such urges occur.

Patients may also develop orthostatic hypotension, potentially accompanied by symptoms such as dizziness, nausea, fainting/blackouts, and sweating. Because hypotension may occur more frequently during initial therapy, patients should be cautioned against rising rapidly after sitting or lying down during this period.