FDA批准Neupro贴用于早期帕金森症的治疗.
美国食品药品管理局(FDA)今天宣布批准Neupro(罗替戈汀透皮传递系统), 一种用于治疗早期帕金森症症状的皮肤贴剂.
罗替戈汀是一种之前未在美国批准的药物, 而Neupro则是第一个批准用于治疗帕金森症症状的透皮贴剂.
帕金森症属于一组运动系统失调的状态, 是由多巴胺生成脑细胞缺失造成的.罗替戈汀是一种多巴胺受体激动剂类药物, Neupro贴剂采用硅酮作为基质, 使药物透过皮肤(透皮)连续地传递输送,该贴剂每24小时替换一次.多巴胺受体激动剂通过激活体内的多巴胺受体, 模拟多巴胺神经递质的作用.
Neupro的药效通过一个固定剂量的响应试验和两个多剂量的试验展示. 平行组研究是随机,双盲且安慰剂控制的, 该研究涉及1154名不使用其它帕金森药物的早期帕金森症患者.
Neupro最常见的不良反应包括粘贴位置的皮肤反应, 头晕,恶心,呕吐,嗜睡和失眠,其中多数均为此类药物的典型不良反应.其它潜在的安全方面的考虑包括从事常规活动(例如驾驶,操作机械)时突发睡眠, 幻觉, 以及站立低压(体位性低血压).
Neupro贴剂由北卡罗来纳州三角公园的施瓦茨生物科学研究公司生产.
部份中文Neupro处方资料（仅供参考）
學名:
Rotigotine
商品牌子名:
Neupro®
剂型及份量：
皮肤渗透性系统贴剂(每贴片含2毫克/ 4毫克/ 6毫克/ 8毫克)
用途及药理：
罗替高停(Rotigotine)为非麦角类多巴胺受体刺激药，具有刺激脑部多巴胺受体的作用，用作柏金逊症的单一治疗或与左旋多巴共用。
使用方法：
只供外用，不可内服。
每天使用一次，24小时后更换另一块新贴片。
请将贴片贴于清洁、较少毛发及干爽的皮肤，如腹部、上手臂、大腿等等。
先把一半的保护贴移除，然后贴上皮肤，再移除另一半保护贴，用手按住皮肤上的贴片约30秒。贴好贴片后记得清洗双手。
更换贴片时，应清洗皮肤及转换新贴片于皮肤上所贴的位置，留意请勿于两星期内将贴片贴于皮肤上同一位置。
副作用:
最常见为贴片位置的皮肤有可能会引起敏感反应。
其他的副作用如头晕，头痛，突发性昏睡，失眠，肠胃不适，便秘，体位性低血压等。
注意事项:
- 贴片不能剪开一半，及避免贴片直接受热，以免影响贴片内药物的渗透速度，后果严重。
- 不要用手接触贴片的黏贴面。
- 如果贴片掉落，请更换另一块贴片，在平日更换贴片的时间再次更换贴片。
- 若然贴片边沿有剥落情况，可用胶纸或胶布贴着边缘位置，以防止贴片掉落。
- 更换贴片时，请把旧贴片对叠，贴上皮肤的那边向内，以免贴片内的药物外泄，然后放回原来的包装袋内弃置于垃圾筒内。
- 由于贴片含有金属铝，如要接受磁力共振造影检查(MRI)或电击心律恢复急救(Cardioversion)前，必先移除贴片，以免因电流通过所产生的热力引致烧伤贴片所贴的皮肤。
药物相互作用:
- 一些抑制大脑中枢神经的药物，如安眠药、抗抑郁药、镇定剂等等，会增强了罗替高停对大脑影响的副作用。
- 另外，部份精神科药物亦会减低了罗替高停的药效，病人应先资询医生或药剂师的意见。
忘记服药:
若忘记更换贴片，请在发现后尽快更换，并于平日正常更换贴片的时间照常再次更换。
储存方法：
应存放于雪柜内，保持在2℃ - 8℃。
UCB公司近日表示Neupro（罗替戈汀透皮贴剂，rotigotine）在欧洲可用于所有的原发性帕金森症，之前Neupro在欧洲批准单用于早期原发性帕金森症，或与左旋多巴联用于晚期帕金森症；此外该药还批准用于成人中到重度原发性腿不宁综合症(RLS)。
公司表示对Neupro可用于所有帕金森症患者与新批准用于腿不宁综合症感到高兴。2008年6月份欧洲要求Neupro仅可用于已在使用该药，并用能保证有冷链支持的从储存、递送到使用的患者群，现在公司在该药的使用全程完成了冷链支持。
Neupro® (Rotigotine Transdermal Patch)
This section provides a summary of the drug information for Neupro® (Rotigotine Transdermal Patch). It is still important that you read the full package leaflet that accompanies the product carefully before you start to take any medication. If you have any further questions about your PD medication, or other aspects of your PD treatment, you should discuss these with your doctor or other healthcare professional.
What is Neupro®?
Neupro® is a medicine for the treatment of Parkinson’s disease. It belongs to a class of treatments called dopamine agonists.
Neupro® works by continuously releasing its active substance rotigotine through the patient’s skin into the body.
Neupro® Availability
Neupro® is currently available in the following countries:
Availability - Formulation
Neupro® is a thin, matrix-type, square-shaped transdermal patch with rounded edges, consisting of three layers. The outside of the backing layer is tan-coloured and imprinted with Neupro 2 mg/24 h, 4 mg/24 h, 6 mg/24 h, or 8 mg/24 h, respectively.
Although four different patch sizes are available, different combinations of these patches can give up to 8 different doses.
Who is suitable for this treatment?
Neupro® is suitable for all stages of idiopathic Parkinson’s disease patients.
Neupro® can offer an alternative to conventional oral therapies. Due to its transdermal administration and specific metabolism and excretion may be of benefit in patients with difficulties swallowing, delayed gastric emptying and resorption of PD medication, undergoing central anaesthesia and dialysis.
Therapeutic indication
Neupro® is indicated for the treatment of the signs and symptoms of early-stage idiopathic Parkinson’s disease as monotherapy (i.e. without levodopa) or in combination with levodopa, i.e. over the course of the disease, through to late stages when the effect of levodopa wears off or becomes inconsistent and fluctuations of the therapeutic effect occur (end of dose or ‘on-off’ fluctuations).
Contra-indications (When not to use)
Hypersensitivity to the active substance or to any of the excipients.
Magnetic resonance imaging or cardioversion (see section “special warning & precautions for use”)
How To take
How to apply the patch
You should stick a Neupro® patch onto the skin once a day. You should leave the patch on your skin for 24 hours and then replace it with a new one. Make sure that you take the old patch off before sticking on the new one. You should replace the patch at around the same time every day.
Put the sticky side of the patch onto clean, dry, healthy skin on the following areas:
shoulder
upper arm
belly
thigh
hip
flank (your side, between your ribs and your hip).
To help avoid skin irritation, stick Neupro® onto a different area of skin each day (for example, on the right side of your body one day, then on the left side the next day and on your upper body one day, then on your lower body). You should not stick Neupro® on the same area of skin twice within 14 days.
It is recommended to apply and maintain gentle pressure with the palm of the hand on the patch for at least one minute or until proper adhesion.
For application instructions, please see downloads section of this page on the EPDA website.
How to store
Neupro® must be stored in a refrigerator (at a temperature of between 2ºC and 8ºC).
It is not necessary to transport Neupro® patches in a special container and they must not be stored in a freezer compartment.
To apply the patch, there is no need to have it reach room temperature, though this will increase patient comfort. In any case, it is recommended to apply and maintain gentle pressure with the palm of the hand on the patch for at least one minute for proper adhesion.
The storage conditions are intended to reduce the possible occurrence of crystallisation of the active substance which has been reported in patches of Neupro® (see EPDA News item: Neupro® recall (27 March 2008).
Special warning & precautions for use
If a patient is insufficiently controlled while on treatment with rotigotine switching to another dopamine agonist might provide additional benefit.
The backing layer of Neupro® contains aluminium. To avoid skin burns, Neupro should be removed if the patient has to undergo magnetic resonance imaging (MRI) or cardioversion.
Dopamine agonists are known to impair the systemic regulation of the blood pressure resulting in postural/orthostatic hypotension. These events were also observed during treatment with Neupro®, however the incidence was similar to that in placebo-treated patients.
Syncope was observed in association with Neupro®, but also at a similar rate in patients treated with placebo.
It is recommended to monitor blood pressure, especially at the beginning of treatment, due to the general risk of orthostatic hypotension associated with dopaminergic therapy.
Neupro® has been associated with somnolence and episodes of sudden sleep onset, particularly in patients with Parkinson’s disease. Sudden onset of sleep during daily activities, in some cases without awareness of any warning signs, has been reported. Prescribers should continually reassess patients for drowsiness or sleepiness, as patients may not acknowledge drowsiness or sleepiness until directly questioned. A reduction of dosage or termination of therapy should be carefully considered.
Pathologic gambling, increased libido and hypersexuality have been reported in patients treated with dopamine agonists for Parkinson’s disease, including Neupro®.
Although not reported with Neupro®, symptoms suggestive of neuroleptic malignant syndrome have been reported with abrupt withdrawal of dopaminergic therapy. Therefore it is recommended to taper treatment.
Hallucinations have been reported and patients should be informed that hallucinations can occur.
Fibrotic complications: Cases of retroperitoneal fibrosis, pulmonary infiltrates, pleural effusion, pleural thickening, pericarditis and cardiac valvulopathy have been reported in some patients treated with ergot-derived dopaminergic agents. While these complications may resolve when the drug is discontinued, complete resolution does not always occur.
Although these adverse events are believed to be related to the ergoline structure of these compounds, whether other, nonergot derived dopamine agonists can cause them is unknown.
Neuroleptics given as antiemetic should not be given to patients taking dopamine agonists.
Ophthalmologic monitoring is recommended at regular intervals or if vision abnormalities occur.
External heat (excessive sunlight, heating pads and other sources of heat such as sauna, hot bath) should not be applied to the area of the patch.
Application site skin reactions may occur and are usually mild or moderate in intensity. It is recommended that the application site should be rotated on a daily basis (e.g. from the right side to the left side and from the upper body to the lower body). The same site should not be used within 14 days. If application site reactions occur which last for more than a few days or are persistent, if there is an increase in severity, or if the skin reaction spreads outside the application site, an assessment of the risk/benefit balance for the individual patient should be conducted.
If there is a skin rash or irritation from the transdermal system, direct sunlight on the area should be avoided until the skin heals. Exposure could lead to changes in the skin color.
If a generalised skin reaction (e.g. allergic rash, including erythematous, macular, papular rash or pruritus) associated with the use of Neupro is observed, Neupro® should be discontinued.
Caution is advised when treating patients with severe hepatic impairment, which may result in lower rotigotine clearance. Neupro® has not been investigated in this patient group. A dose reduction might be needed in case of worsening of the hepatic impairment. Unexpected accumulation of rotigotine levels may also occur at acute worsening of renal function.
The incidence of some dopaminergic adverse events, such as hallucinations, dyskinesia, and peripheral oedema generally is higher when given in combination with L-dopa. This should be considered when prescribing rotigotine.
In clinical studies, the 6 month-specific rates of peripheral edema remained at about 4% through the entire observation period up to 36 months.
Top of page Interactions with other medicinal products
Because rotigotine is a dopamine agonist, it is assumed that dopamine antagonists, such as neuroleptics (e.g. phenothiazines, butyrophenones, thioxanthenes) or metoclopramide, may diminish the effectiveness of Neupro®, and co-administration should be avoided. Because of possible additive effects, caution should be advised when patients are taking sedating medicinal products or other CNS (central nervous system) depressants (e.g. benzodiazepines, antipsychotics, antidepressants) or alcohol in combination with rotigotine.
Co-administration of omeprazole (inhibitor of CYP2C19), in doses of 40 mg/day, had no effect on the pharmacokinetics and metabolism of rotigotine in healthy volunteers.” to maintain consistency with our current product licence.
Co-administration of L‑dopa and carbidopa with rotigotine had no effect on the pharmacokinetics of rotigotine, and rotigotine had no effect on the pharmacokinetics of L‑dopa and carbidopa.
Neupro® may potentiate the dopaminergic adverse reaction of L-dopa and may cause and/or exacerbate pre-existing dyskinesia, as described with other dopamine agonists.
Pregnancy & lactation
Ask your doctor or pharmacist for advice before taking any medicine.
There are no adequate data from the use of Neupro® in pregnant women. Animal studies do not indicate any teratogenic effects in rats and rabbits, but embryo-toxicity was observed in rats and mice at materno-toxic doses. The potential risk for humans is unknown. Rotigotine should not be used during pregnancy.
Because rotigotine decreases prolactin secretion in humans, inhibition of lactation is expected. Studies in rats have shown that rotigotine and/or its metabolite(s) is excreted in breast milk. In the absence of human data, breast-feeding should be discontinued.
Top of page Effects on ability to drive & use machines
Rotigotine may have major influence on the ability to drive and use machines.
Patients being treated with rotigotine and presenting with somnolence and/or sudden sleep episodes must be informed not to drive or engage in activities (e.g. operating machines) where impaired alertness may put themselves or others at risk of serious injury or death until such recurrent episodes and somnolence have resolved.
Top of page Possible undesirable effects
Like all medicines, Neupro® can cause side effects, although not everybody gets them.
Side effects that occur frequently are those due to the central neuropharmacological activity of dopamine agonists or due to being a transdermal patch.
Very common side effects (affects more than 1 user in 10)
sleepiness, dizziness, headache
feeling sick (nausea), vomiting
skin irritations under the patch such as redness and itching
Common side effects (affects 1 to 10 users in 100)
seeing or hearing things that are not real (hallucinations)
difficulty falling asleep, sleep disorder, difficulty sleeping, nightmare, unusual dreams
loss of consciousness, involuntary movements related to Parkinson’s disease (dyskinesia), feeling dizzy when standing up because of fall in blood pressure
vertigo (sensation of whirling motion)
feeling of heartbeat (palpitation)
low blood pressure when standing up, high blood pressure
hiccups
constipation, dry mouth, heartburn
redness, increased sweating, itching
swelling of legs and feet
feeling weak, feeling tired
falling
weight loss
Uncommon side effects (affects 1 to 10 users in 1,000)
allergic reaction
falling asleep suddenly without warning
abnormal thinking about reality and behaviour
increased sex drive, inability to resist the impulse to perform an action that is harmful involving excessive gambling and repetitive meaningless actions
confusion
blurred vision
visual disturbances such as seeing colours or lights
abnormal heart rhythm
low blood pressure
stomach discomfort and pain
generalised itching, skin irritation
unable to achieve or maintain an erection
increased or abnormal liver function test results
weight increase
increased heart rate
Rare side effects (affects 1 to 10 users in 10,000)
psychotic disorders
unwanted and uncontrolled thoughts and behaviours
involuntary muscle spasms (convulsion)
generalised rash
irritability
Overdose
The most likely adverse reactions would be those related to the pharmacodynamic profile of a dopamine agonist, including nausea, vomiting, hypotension, involuntary movements, hallucinations, confusion, convulsions and other signs of central dopaminergic stimulation.
There is no known antidote for overdose of dopamine agonists. In case of suspected overdose, the patch(es) should immediately be removed from the patient. Levels of rotigotine decrease after patch removal.
The patient should be monitored closely, including heart rate, heart rhythm and blood pressure. Because rotigotine is over 90% protein bound, dialysis would not be expected to be beneficial. Treatment of overdose may require general supportive measures to maintain the vital signs.
The terminal half-life of rotigotine is 5 to 7 hours.
Pharmacological properties
Rotigotine is a non-ergolinic D3/D2/D1 dopamine agonist for the treatment of Parkinson’s disease. It is believed to elicit its beneficial effect by activation of the D3, D2 and D1 receptors of the caudate-putamen in the brain.
Rotigotine alleviates signs and symptoms of idiopathic Parkinson’s disease.
The effectiveness of Neupro® in the treatment of the signs and symptoms of idiopathic Parkinson's disease was evaluated in a multinational drug development program consisting of four pivotal, parallel, randomized, double-blind placebo controlled studies.
Two trials investigating the effectiveness of Neupro® in the treatment of the signs and symptoms of idiopathic Parkinson’s disease were conducted in patients who were not receiving concomitant dopamine agonist therapy and were either L-dopa naïve or previous L-dopa treatment was ≤ 6 months. The primary outcome assessment was the score for the Activities of Daily Living (ADL) component (Part II) plus the Motor Examination component (Part III) of the Unified Parkinson’s Disease Rating Scale (UPDRS).
Two additional trials were conducted in patients who were receiving concomitant levodopa therapy. The primary outcome assessment was the reduction in “off” time (hours). Efficacy was determined by the subject’s response to therapy in terms of responder and absolute improvement in the time spent “off”.
Special patient groups
Because therapy with Neupro® is initiated at a low dose and gradually titrated according to clinical tolerability to obtain the optimum therapeutic effect, adjustment of the dose based on gender, weight, or age is not necessary.
Product information downloads
The information on this pageprintout is a general summary of the Neupro® transdermal patch medication product.
Please click on the links below to download more detailed information on the specific Neupro® medication, its handling and use. Links go to the electronic Medicines Compendium (eMC) website.
Further detailed information on the specific Neupro® medication, its handling and use can be downloaded via the electronic Medicines Compendium (eMC) website (http://emc.medicines.org.uk/):
UK Patient Information Leaflets (PIL)
Neupro® 2mg/24 hr Transdermal Patch PIL
Neupro® 4mg/24 hr Transdermal Patch PIL
Neupro® 6mg/24 hr Transdermal Patch PIL
Neupro® 8mg/24 hr Transdermal Patch PIL
Neupro® Treatment Initiation Pack PIL
UK Summary of Product Characteristics (SPC)
Please note that SPCs are designed for healthcare professionals.
Neupro® 2mg/24 hr Transdermal Patch SPC
Neupro® 4mg/24 hr Transdermal Patch SPC
Neupro® 6mg/24 hr Transdermal Patch SPC
Neupro® 8mg/24 hr Transdermal Patch SPC
Neupro® Treatment Initiation Pack SPC
European Public Assessment Report
Further detailed information can also be downloaded via the European Medicines Agency (EMEA) website (www.emea.europa.eu):