AMPYRA（dalfampridine）缓释片剂，10毫克经美国食品和药物管理局（FDA）批准，以帮助改善成人多发性硬化症（MS）患者的行走。
AMPYRA是第一个也是唯一一个经FDA特别批准用于此用途的品牌处方MS疗法。美国有超过40万人和全世界近250万人患有MS，而对于大多数人来说，这种疾病会影响他们的行走能力。
批准日期：2010年1月22日 公司：Acorda Therapeutics
AMPYRA（达方吡啶 dalfampridine）缓释片，用于口服
美国最初批准：2010年
作用机制
达氟嘧啶发挥其治疗作用的机制尚未完全阐明。 Dalfampridine是一种广谱钾通道阻滞剂。 在动物研究中，dalfampridine已被证明通过抑制钾通道增加脱髓鞘轴突中动作电位的传导。
适应症和用法
AMPYRA（dalfampridine）是一种钾通道阻滞剂，用于改善成人多发性硬化症（MS）患者的行走。步行速度的提高证明了这一点
剂量和给药
最大推荐剂量为每天两次10mg（间隔约12小时）。没有证据表明每日两次剂量大于10毫克的额外益处。包括癫痫发作在内的不良反应在较高剂量时更常见。
带或不带食物。管理整个平板电脑;不分裂，粉碎，咀嚼或溶解。
如果错过剂量，患者不应服用双倍或额外剂量。
在开始用AMPYRA治疗之前，应该知道估计的肌酐清除率（CrCl）。对于轻度肾功能不全（CrCl 51-80mL/min）的患者，AMPYRA可能达到与癫痫发作风险相关的血浆水平，应仔细考虑AMPYRA的潜在益处，以防止这些患者癫痫发作的风险。
剂量形式和强度
10毫克片剂
禁忌症
癫痫病史
中度或重度肾功能损害（CrCl≤50mL/min）
对AMPYRA或4-氨基吡啶过敏的历史
警告和注意事项
AMPYRA可导致癫痫发作;随着AMPYRA剂量的增加，癫痫发作的风险增加;停止AMPYRA并且如果发生癫痫发作则不重新启动。
避免与其他形式的4-氨基吡啶（4-AP，氨吡啶）同时使用，因为活性成分是相同的。
AMPYRA可引起过敏反应。如果发生这种情况，请停止并重新启动AMPYRA。
不良反应
AMPYRA最常见的不良事件（发生率≥2％，速度大于安慰剂率）是尿路感染，失眠，头晕，头痛，恶心，虚弱，背痛，平衡障碍，多发性硬化复发，感觉异常，鼻咽炎，便秘，消化不良和咽喉疼痛。
药物相互作用
OCT2抑制剂：伴随使用可能导致暴露增加和癫痫发作的潜在风险。
用于特定人群
怀孕：根据动物数据，可能会造成胎儿伤害。
护理母亲：考虑到药物对母亲的重要性，停止使用药物或护理。
老年人使用：由于老年患者更可能降低肾功能，因此在开始AMPYRA治疗之前了解这些患者的估计CrCl尤为重要。
包装提供/存储和处理
AMPYRA（dalfampridine）延长释放片剂，10毫克是薄膜包衣，白色到灰白色，双凸面，椭圆形，无刻痕的片剂，平边。 片剂通过一侧的凹陷代码“A10”识别，并且以60瓶的形式提供。
NDC 10144-427-60瓶60粒
储存在25°C（77°F）。 短途旅行允许15°C至30°C（59°F至86°F）。
Ampyra(Dalfampridine Extended-Release Tablets)
DESCRIPTION
AMPYRA (dalfampridine) is a potassium channel blocker, available in a 10 mg tablet strength. Each tablet contains 10 mg dalfampridine, formulated as an extended release tablet for twice-daily oral administration. Dalfampridine is also known by its chemical name, 4-aminopyridine.
CLINICAL PHARMACOLOGY
Mechanism of action
The mechanism by which dalfampridine exerts its therapeutic effect has not been fully elucidated. Dalfampridine 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.
Pharmacodynamics
AMPYRA does not prolong the QTc interval and does not have a clinically important effect on QRS duration.
Pharmacokinetics
Absorption and Distribution:
Orally administered dalfampridine is rapidly and completely absorbed from the gastrointestinal tract. Absolute bioavailability of extended release AMPYRA tablets has not been assessed, but relative bioavailability is 96% when compared to an aqueous oral solution. The extended release tablet delays absorption of dalfampridine relative to the solution formulation, giving a slower rise to a lower peak concentration (Cmax), with no effect on the extent of absorption (AUC). Single AMPYRA tablet 10 mg doses administered to healthy volunteers in a fasted state gave peak concentrations ranging from 17.3 ng/mL to 21.6 ng/mL occurring 3 to 4 hours post-administration (Tmax). In comparison, Cmax with the same 10 mg dose of dalfampridine in an oral solution was 42.7 ng/mL and occurred approximately 1.3 hours after dosing. Exposure increased proportionally with dose.
Dalfampridine is largely unbound to plasma proteins (97-99%). The apparent volume of distribution is 2.6 L/kg.
There is no apparent difference in pharmacokinetic parameter values following administration of AMPYRA tablets to either healthy volunteers or patients with MS.
When dalfampridine is taken with food, there is a slight increase in Cmax (12-17%) and a slight decrease in AUC (4-7%). These changes in exposure are not clinically significant, and therefore the drug may be taken with or without food [see Dosage and Administration].
Metabolism and Elimination:
Dalfampridine and metabolites elimination is nearly complete after 24 hours, with 95.9% of the dose recovered in urine and 0.5% recovered in feces. Most of the excreted radioactivity in urine was parent drug (90.3%). Two metabolites were identified: 3-hydroxy-4-aminopyridine (4.3%) and 3-hydroxy-4-aminopyridine sulfate (2.6%). These metabolites have been shown to have no pharmacologic activity on potassium channels.
The elimination half-life of dalfampridine following administration of the extended release tablet formulation of AMPYRA is 5.2 to 6.5 hours. The plasma half-life of the sulfate conjugate is approximately 7.6 hours and the half-life of 3-hydroxy-4-aminopyridine could not be calculated because concentrations for most subjects were close to or below the limit of quantitation.
In vitro studies with human liver microsomes indicate that CYP2E1 was the major enzyme responsible for the 3-hydroxylation of dalfampridine. The identity of the CYP enzymes suspected of playing a minor role in the 3-hydroxylation of dalfampridine could not be established unequivocally
INDICATIONS AND USAGE 
AMPYRA™ (dalfampridine) is a potassium channel blocker indicated to improve walking in patients with multiple sclerosis (MS). This was demonstrated by an increase in walking speed
CONTRAINDICATIONS
-History of seizure
-Moderate or severe renal impairment
PRECAUTIONS
WARNINGS AND PRECAUTIONS
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 (CrClleq50 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.
AMPYRA should not be taken with other forms of 4-aminopyridine (4-AP, fampridine), since the active ingredient is the same.
Urinary tract infections were reported more frequently as adverse reactions in patients receiving AMPYRA 10 mg twice daily compared to placebo.
USE IN SPECIFIC POPULATIONS
Pregnancy: Based on animal data, may cause fetal harm.
Nursing Mothers: Discontinue drug or nursing taking into consideration importance of drug to mother.
Pediatric use: Safety and effectiveness of AMPYRA in patients younger than 18 years of age have not been established
Renal Impairment: Clearance of dalfampridine is decreased in patients with renal impairment; AMPYRA is contraindicated in patients with moderate or severe renal impairment (CrClleq50 mL/min); AMPYRA plasma levels in patients with mild renal impairment (CrCl 51-80 mL/min) may approach those seen at a dose of 15 mg twice daily, a dose which may be associated with an increased risk of seizures.
Geriatric use: Because elderly patients are more likely to have decreased renal function, it is particularly important to know the estimated CrCl in these patients before initiating AMPYRA treatment
ADVERSE REACTIONS
 The most common adverse events (incidence  geq2% 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.
DOSAGE AND ADMINISTRATION 
Maximum recommended dose: 10 mg twice daily (approximately 12 hours apart) with or without food.
Patients should not take double or extra doses if a dose is missed. No additional benefit was demonstrated at doses greater than 10 mg twice daily and adverse events, including seizures, were more frequent at higher doses.
Tablets should only be taken whole; do not divide, crush, chew, or dissolve.
Renal impairment: AMPYRA is contraindicated in patients with moderate or severe renal impairment; the risk of seizures in patients with mild renal impairment 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.
HOW SUPPLIED
MPYRA (dalfampridine) extended release tablets, 10mg are a film-coated, white to off-white, biconvex, oval shaped, non-scored tablets with flat edge. The tablets are identified by a debossed code “A10” on one side and are available in bottles of 60.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=550eb76a-e4a6-4fa1-ad65-c0fd8b0ce783