美国食品药品管理局近日批准Ampyra（dalfampridine）缓释片用于提高多发性硬化症（MS）患者的步行速度。该药品是首个获批用于这一用途的药物。
MS是一种能够影响人类中枢神经系统--大脑、脊髓和视神经，从而致残的慢性疾病。美国大约有40万MS患者，全球约有2500万MS患者。MS的病程进展、严重程度和症状是不可预知的，并且不同患者的情况也可能会互不相同。有些患者的症状可能是轻度的，如四肢麻木；有些患者的症状可能是严重的，如麻痹或失明。虽然这些症状常常较轻微且易被忽略，但大约一半的MS患者都曾有过认知缺损的经历，例如在注意力、记忆和判断方面存在困难。MS患者中也常会出现抑郁症状。
FDA药品审评与研究中心神经病学产品部主任、医学博士Russell Katz说，“MS患者面对的最重要的问题之一是行走困难。”
临床试验显示，接受Ampyra治疗的患者步行速度比接受安慰剂治疗的患者步行速度更快。最常见的不良反应包括泌尿道感染、失眠、头晕、头痛、恶心、虚弱、背痛、平衡障碍、鼻咽肿胀、便秘、腹泻、消化不良、咽喉痛、发烧、注射部位麻刺感或瘙痒。当所用Ampyra剂量超过推荐剂量（10毫克，每天两次）时，可能会引起癫痫发作。患有中度或严重肾脏疾病的患者应禁止使用Ampyra。
AMPYRA
Manufacturer:
Acorda Therapeutics
Pharmacological Class:
Potassium channel blocker
Active Ingredient(s):
Dalfampridine 10mg; ext-rel tabs.
Indication(s):
To improve walking in patients with multiple sclerosis (demonstrated by an increase in walking speed).
Pharmacology:
In patients with multiple sclerosis (MS), the functioning of nerve fibers in the central nervous system degrades over time, causing, among other symptoms, difficulties in ambulation. Research has shown that 64–85% of people with MS have difficulty walking, and 70% of those affected report it to be the most challenging aspect of their disease. Within 15 years of a diagnosis of MS, 1/2 of the patients often need help walking and, in later stages, up to 1/3 are unable to walk.
Dalfampridine, which was previously known as fampridine, is a broad spectrum potassium channel blocker. In animal studies, dalfampridine has been shown to increase conduction of action potentials in demyelinated axons through inhibition of potassium channels. The mechanism of action in humans has not been fully elucidated.
Elevated serum levels of dalfampridine can result in seizures. Because this drug is eliminated unchanged by the kidneys, renal function must be assessed before starting therapy, and the recommended dose should not be exceeded.
Clinical Trials:
The effectiveness of dalfampridine in improving ambulation was evaluated in two trials involving 540 patients with MS. The mean duration of disease in these patients was 13 years, and the mean Kurtzke Expanded Disability Status Scale score was 6.
In trial 1, a randomized, 21-week placebo-controlled parallel-group study, the study drug dosed at 10mg twice daily was compared to placebo. The primary efficacy measure was walking speed as assessed by the Timed 25-foot Walk, using a responder analysis. “Responders” were defined as those who showed faster walking speeds for at least 3 visits out of a possible 4 during the double-blind period than the maximum value achieved in the 5 non-double-blind, no-treatment visits. Of 301 patients enrolled, 283 completed all study visits. Trial 2 was a 14-week randomized, placebo-controlled, parallel-group study that enrolled 239 patients, 227 of whom completed all study visits. In each trial, a significantly greater proportion of patients taking dalfampridine were responders compared to those given placebo. In trial 1, 34.8% of patients given dalfampridine were responders, compared to 8.3% for those given placebo. In trial 2, 42.9% of patients given the study drug were responders, compared to 9.3% for placebo.
A significantly greater proportion of patients taking the study drug had increases in walking speed of at least 10%, 20% or 30% from baseline.
Legal Classification:
Rx
Adults:
Swallow whole. ≥18yrs: 10mg every 12 hours.
Children:
<18yrs: not recommended.
Contraindication(s):
History of seizures. Moderate to severe renal impairment (CrCl ≤ 50mL/min). Concomitant other forms of 4-aminopyridine.
Warnings/Precautions:
Mild renal impairment (CrCl 51–80mL/min) (increased seizure risk). Pregnancy (Cat.C). Labor & delivery. Nursing mothers: not recommended.
Adverse Reaction(s):
UTI, insomnia, dizziness, headache, GI upset, asthenia, back pain, balance disorder, MS relapse, paresthesia, nasopharyngitis, constipation, throat pain; seizures (possible at higher doses).
Notes:
AMPYRA will be distributed exclusively through specialty pharmacies. For more information, call AMPYRA Patient Support Services at (888) 881–1918.
How Supplied:
Tabs—60
Last Updated:
4/7/2010
美FDA批准达方吡啶改善多发性硬化病患者的行走能力
日前，美国FDA批准了Acorda治疗学有限公司开发的达方吡啶缓释片（dalfampridine／Ampyra），用于治疗多发性硬化病患者以改善行走能力。这是FDA首次批准用于此用途的药。达方吡啶可以单用，也能与现有多发性硬化病治疗药物、包括免疫调节剂联合使用。临床研究已经证实，使用达方吡啶治疗能够提高多发性硬化病患者的行走速度，且其对所有4种主要多发性硬化病亚型（复发-缓解型、继发性进行性、进行性一复发型和原发性进行性）均有效。
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What Is AMPYRA® (dalfampridine) Extended Release Tablets?
AMPYRA® (dalfampridine) Extended Release Tablets is indicated as a treatment to improve walking in patients with multiple sclerosis (MS). This was demonstrated by an increase in walking speed.
First in a new class of approved MS agents.
Shown to increase conduction through inhibition of potassium channels in animal studies. The mechanism by which AMPYRA (dalfampridine) exerts its therapeutic effect has not been fully elucidated.
AMPYRA improved walking speed in significantly more patients than placebo in 2 clinical trials (34.8% vs. 8.3% and 42.9% vs. 9.3%), p < 0.001 in both.
Improved walking in patients in two Phase 3 clinical trials:
Across the major types of MS.
With or without use of immunomodulatory drugs including interferons, glatiramer acetate, or natalizumab.
With no differences in effectiveness detected based on degree of impairment, age, gender or body mass index.
In EDSS scores ranging from 2.5 to 7.0.6
Oral administration
Indication
AMPYRA® (dalfampridine) Extended Release Tablets is indicated as a treatment to improve walking in patients with multiple sclerosis (MS). This was demonstrated by an increase in walking speed.
IMPORTANT SAFETY INFORMATION
The use of AMPYRA is contraindicated in the following conditions: History of seizure, or moderate or severe renal impairment.
AMPYRA should not be taken with other forms of 4-aminopyridine (4-AP, fampridine), since the active ingredient is the same.
Patients should discontinue use of any product containing 4-aminopyridine prior to initiating treatment with AMPYRA in order to reduce the potential for dose-related adverse reactions, including seizures.
Seizures: AMPYRA can cause seizures. The risk of seizures increases with increasing AMPYRA doses. AMPYRA is contraindicated in patients with a prior history of seizure. Discontinue AMPYRA use if seizure occurs.
Renally impaired patients: AMPYRA is contraindicated in patients with moderate or severe renal impairment (CrCl ≤ 50 mL/min); the risk of seizures in patients with mild renal impairment (CrCl 51-80 mL/min) is unknown, but AMPYRA plasma levels in these patients may approach those seen at a dose of 15 mg twice daily, a dose that may be associated with an increased risk of seizures; estimated CrCl should be known before initiating treatment with AMPYRA.
Urinary tract infections were reported more frequently as adverse reactions in patients receiving AMPYRA 10 mg twice daily compared to placebo.
The most common adverse events (incidence ≥ 2% and at a rate greater than the placebo rate) for AMPYRA in MS patients were urinary tract infection, insomnia, dizziness, headache, nausea, asthenia, back pain, balance disorder, multiple sclerosis relapse, paresthesia, nasopharyngitis, constipation, dyspepsia, and pharyngolaryngeal pain.
The risk of adverse events, including seizures, increases with increasing AMPYRA doses. No additional benefit was demonstrated at doses greater than 10 mg twice daily.
There are no adequate and well-controlled studies of AMPYRA in pregnant women. AMPYRA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Safety and effectiveness of AMPYRA in patients younger than 18 years of age have not been established.
Clinical studies of AMPYRA did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.
For more information, please see the complete Prescribing Information, including the Medication Guide.
You are encouraged to report negative side effects of prescription drugs to the FDA.
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原产地英文商品名:
AMPYRA ER TABS 10mg/tab 60tabs/bottle
原产地英文药品名:
DALFAMPRIDINE
中文参考商品译名:
AMPYRA缓释片 10毫克/片 60片/瓶
中文参考药品译名:
达方吡啶
生产厂家中文参考译名:
阿索尔达
生产厂家英文名:
ACORDA