英文药名: Sinemet CR(Carbidopa/Levodopa Sustained Release Tablets) 中文药名: 息宁（卡比多巴~左旋多巴缓释片） 生产厂家: Not available 规格 心宁美，(息宁控释片Sinemet)： 卡比多巴25mg+左旋多巴100mg 卡比多巴10mg+左旋多巴100mg 卡比多巴50mg+左旋多巴200mg 卡比多巴50mg+左旋多巴250mg 药品名称 药物名称：息宁 英文名：Sinemet 别名：息宁，心宁美, 卡比多巴-左旋多巴, 息宁控释片, 帕金宁控释片 外文名：Carbidopa and Levodopa, Sinemet 类别：抗帕金森病药 药理毒理 神经内科用药。 本药是卡比多巴(一种芳香氨基酸类脱羧酶抑制剂)与左旋多巴(多巴胺的前体药物)的复合物，是以聚合物为基质的控释片剂。左旋多巴在脑内通过脱羧形成多巴胺而缓解帕金森氏病的症状。不能透过血脑屏障的卡比多巴只抑制外周左旋多巴的脱羧，从而使更多的左旋多巴转运到脑，转化成多巴氨，避免了左旋多巴频繁大剂量给药的必要性。低剂量减少或可能有助于消除胃肠道和心血管系统的副作用，尤其是那些与外周形成多巴胺有关的副作用。控释片在4-6小时内释放出有效成分。本药的血浆左旋多巴水平变化较小。 适应症 震颤麻痹，震颤麻痹综合征。 用法用量 口服，0.5～1片/次，2～4次/日，按病情需要逐渐增量，一般每日不超过卡比多巴75mg，左旋多巴750mg。 任何疑问，请遵医嘱！ 不良反应 常见运动障碍、恶心、呕吐、抑郁、失眠和幻觉等，偶有消化道出血。 药物相互作用 与单胺氧化酶抑制药合用可致血压骤升。 吩塞秦、可乐定、罂粟碱、利舍平、苯妥英等可拮抗本品的作用。 溴隐亭可增强本品作用。 注意事项 妊娠C类。狭角型青光眼、皮肤癌患者禁用。 有心、肝、肺、肾、消化道溃疡及精神障碍者慎用 包装规格 注意：以下产品不同规格和不同价格，购买时请以电话咨询为准！ ·100/10mg 100 片(Bristol-Myers Squibb生产) ·100/25mg 90 片(Merck 生产) ·250/25mg 90 片(Merck 生产) --------------------------------------------- ·100mg/10mg 150 片 ·100mg/25mg 150 片 ·250mg/25mg 100 片 ------------------------------------------------- SINEMET 25/100 scored tablets containing 25mg of carbidopa + 100mg of levodopa supplied in bottles of 100. SINEMET 25/250 scored tablets containing 25mg of carbidopa + 250mg of levodopa supplied in bottles of 100. SINEMET CR is a controlled-release formulation of carbidopa, MSD, and levodopa, MSD, in a ratio of 1:4. 50/200mg, tablet SINEMET CR 50/200 is available in bottles of 100 tablets Controlled-release carbidopa/levodopa and immediate-release C/L are equally effective in treating the symptoms of Parkinson's disease. Some patients prefer the controlled-release (CR) formulation due to the convenience of less frequent dosing based on its longer duration of action. After taking carbidopa/levodopa immediate-release for several years, a patient may find that the effect of the medication begins to wear off before it is time for the next dose. One response is to shorten the intervals between doses (or add an additional dose if needed); another choice is to switch from immediate-release C/L to Sinemet CR®. Sinemet CR® contains the same medications as C/L, but is formulated to dissolve gradually in the gut. Composition Sinemet is a combination of Carbidopa, an inhibitor of the aromatic amino-acid decarboxylase enzyme and Levodopa (L-Dopa), the metabolic precursor of Dopamine, and it is used in the treatment of Parkinson's disease and Parkinson's syndrome. Levodopa relieves the symptoms of Parkinson's disease presumably when it becomes decarboxylased to Dopamine in the Brain. Carbidopa, which does not cross the haematoencephalic barrier, is limited to only to the extra cerebral decarboxylation of the Levodopa, thus providing a greater amount of Levodopa to the Brain, for it's subsequent transformation into Dopamine. This eliminates the need for large doses of Levodopa at frequent intervals. The lower dosage, on the other hand, also reduces or eliminates many of the side effects attributed to the Dopamine formed in extra cerebral tissue. Used as prescribed and thanks to it's Levodopa content. Sinemet improves general therapeutic response. It's lower dosage (approximately 80% less than that of Levodopa alone), provides effective and lasting plasmatic concentrations of Levodopa. While it is known that pyridoxine hydrochlorate (Vitamin B6), accelerates the periferic metabolism of Levodopa to Dopamine, Carbidopa inhibits this action. In an experiment in which patients received from 100 to 500mg of pyridoxine on a daily basis, no alteration was seen in the anti- Parkinson effect of the Levodopa, while they were treated with the Carbidopa and Levodopa combination. It has been reported that the combination of Sinemet with the inhibitors of the Monoamine Oxydase B (such as Deprenyl) increases the effectiveness of Sinemet in patients with difficulty or slowness of movement. Clinical Advantages Sinemet usually reduces and in some cases even eliminates side effects frequently suffered by patients undergoing Levodopa therapy- Anorexia, nausea, vomiting. By reducing some of the side effects produced by Levodopa used alone, Sinemet allows a greater number of patients to feel relief from the symptoms of Parkinson's disease. Sinemet provides fast therapeutic relief. Response to Sinemet has been seen in as little as a day's time, often after a single dose. Sinemet minimizes the need for the prolonged individual dosages required in Levodopa treatment. Fully effective dosages are usually carried out within seven days, in contrast to the weeks or months needed for Levodopa. Following the Sinemet treatment, the plasmatic levels from Levodopa are five times greater than those obtained with the same dosage of Levodopa applied on it's own. Subjects responding to Levodopa can receive Sinemet treatment. Sinemet reduces the fluctuations, often seen in the use of Levodopa on it's own, in the patient's response. Sinemet may be used with other anti-Parkinson medicine (see directions). Information for Users Sinemet is recommended for the treatment of Parkinson's disease and Parkinson's syndrome. It is very useful for alleviating Parkinson's syndrome, especially stiffness and bradykinesia. Sinemet is often useful in the treatment of tremors, dysphasia, excessive saliva flow and postural instability, associated with Parkinson's disease or syndrome. When therapeutic response to Levodopa by itself is irregular, and the signs and symptoms of Parkinson's disease do not appear in a uniformly controlled manner during the day, the substitution of Sinemet usually proves to be effective in reducing this fluctuation. By reducing certain side effects produced by the use of Levodopa on it's own. Sinemet enables a greater number of patients to obtain an adequate remission from the symptoms of Parkinson's disease. Sinemet is recommended for patients suffering from Parkinson's disease or syndrome, who have been taking Vitamin complexes containing B6. Directions for Use Sinemet, a combination of both Carbidopa and Levodopa, is available in tablet form. Each Sinemet tablet contains 25mg Carbidopa and 250mg Levodopa. General Considerations The prescribed dosage depends on the individual needs of each patient and this may require an adjustment of either the individual dosage, or the frequency of it's administration. Treatment usually lasts seven days. Studies have shown that the peripheric Dopa-decarboxylase is absorbed by the Carbidopa at a rate of 70-200 mg/ day. Patients who are given less Carbidopa are more likely to suffer nausea and vomiting. Should such an undesired therapeutic effect take place more often with Sinemet than with Levodopa alone, patients should be closely observed during this period of adjustment to the dosage. Involuntary movement especially can occur more rapidly with Sinemet than with Levodopa. The onset of involuntary movement may require a reduction of the dosage. In certain patients the blepharospasm may be a useful early warning sign of excessive dosage. In the case of general anaesthetic, Sinemet may be continued as long as the patient is allowed to take liquids and medicines by mouth. If treatment is temporally interrupted, the regular daily dosage can be administered as soon as the patient is able to take medicine orally. Patients who are Not Receiving Levodopa Treatment The usual dosage is a half tablet of Sinemet once or twice per day. A half tablet may increase this dosage either daily or on alternative days, until optimum results are obtained. Patients Being Treated with Levodopa Levodopa treatment must be interrupted at least 12 hours (24 hours for delayed action Levodopa preparations), prior to starting Sinemet treatment. It should be taken into account that the daily dosage of Sinemet provides approximately 20% of the previous Levodopa dosage. The recommended initial dosage for the majority of patients who take more than 1500mg of Levodopa is one Sinemet tablet three or four times daily. (For example, if the patient takes 4g of Levodopa per day, he should not exceed 3 tablets of Sinemet per day). Patients taking Levodopa together with another decarboxylase inhibitor should stop treatment at least 12 hours before beginning Sinemet treatment. We strongly recommend commencing Sinemet treatment in order to supply the same amount of Levodopa contained in the Levodopa/ decarboxylase inhibitors used previously. Follow up Treatment The majority of patients can continue with a dosage of 3 to 6 tablets per day. There is no benefit to be had by increasing the dosage of Carbidopa beyond 8 tablets of Sinemet 25-250 per day, and the patient is warned against exceeding this maximum dosage. Some patients may need a further dosage of Levodopa. Results show that other anti-Parkinson medication (except Levodopa) may be continued, although the dosage may need to be adjusted. Contraindications Sinemet is not recommended for patients with a known hypersensitivity to this product, who suffer from close angle glaucoma, or who are in the acute phase of myocardial infarction. Since Levodopa can also activate malignant melanoma, it must not be used by patients with suspicious looking undiagnosed cutaneous lesions, or with amanuensis of melanoma. Monoamine Oxydase A inhibitors and Sinemet should not be taken at the same time, and treatment with this inhibitor should be interrupted at least two weeks prior to beginning Sinemet treatment. This product should not be taken by patients younger than 18 years of age, during pregnancy or by nursing mothers. Precautions Sinemet can be taken by patients who have undergone the treatment of Levodopa on it's own, but such treatment of Levodopa must be interrupted at least 12 hours before starting Sinemet. Sinemet must be substituted by a posology which supplies approximately 20% of the Levodopa used previously (see directions for use). Patients being treated with Sinemet must avoid taking additional dosages of Levodopa, except under a doctor's strict supervision. Sinemet is not recommended for the treatment of medicinal drug induced extrapyramidal reactions. Patients known for psychotic behavior or amanuensis should be treated with caution. As with Levodopa, Sinemet may cause involuntary movements and mental disturbances. Patients with a history of serious involuntary movements and psychotic conduct when treated with Levodopa should be closely watched when Sinemet substitutes this. It is thought that such reactions are due to an increase in cerebral Dopamine following the administration of Levodopa and that the use of Sinemet may cause a relapse. All patients should be carefully supervised regarding the development of mental modifications, depression and suicidal tendencies, or other such serious antisocial behavior. The most rapid appearance of high Dopamine levels obtained with Sinemet treatment compared to that of Levodopa alone might cause premature problems of movement. Such disturbances require a reduction in the dosage of Sinemet. Sinemet must be administered with care to asthma, renal, hepatic and endocrine disorders. Attention should be paid to the administration of Sinemet to patients who have a history of arrhythmias. In such patients, cardial functions must be controlled with particular care during the period of dosage adjustment. As with Levodopa, there is a chance of hemorrhaging with patients with a history of peptic ulcers. A complex symptomatology has been reported which is similar to the malignant neuroleptic syndrome with muscular stiffness, high body temperature, mental modifications and the increase in the silky creatine phosphate when the anti- Parkinson treatment is suddenly stopped. Thus the patient should be attentively observed when the Sinemet dosage is suddenly reduced or halted, especially if the patient is being treated with care. As with Levodopa, in the case of prolonged treatment, it is wise to undergo periodic tests, regarding the haematic formula and the hepatic, renal and cardiocirculatory functions. Patients with chronic open angle glaucoma can be treated with caution with Sinemet, providing intra-ocular pressure is controlled and the patient is kept under close observation for signs of change during the treatment. Pharmacological Interaction Close attention should be paid when the following medicines are used simultaneously with Sinemet. It has been proven that when Sinemet is taken together with anti- hypertensive treatment, symptomatic hypertension can occur. Thus, when Sinemet treatment is started, an adjustment in the dosage of the anti- hypertension product may be necessary. There have been reports, although admittedly few, concerning undesirable reactions including hypertension and difficulty in movement, derived from the concomitant use of tricyclic antidepressants and Sinemet. Phenothiazines and butyrophenones may reduce the therapeutic effects of Levodopa. It has also been reported that phenitoine and papaverine also canceled out the beneficial effects of the latter. Patients who take this medication with Sinemet should be carefully advised concerning the eventual loss of its therapeutic properties. Given that Levodopa competes with certain amino acids. Its absorption may be compromised in certain patients by a high protein diet. Side Effects Side effects occurring to patients being treated with Sinemet are related to the central neuropharmacological activity of Dopamine. These can usually be diminished by a reduced dosage. The most common are- brusque, distonic movements and/ or other involuntary movements. Muscular fibrillation and blepharospasm can be considered as warning signs to reduce medication. While Carbidopa allows for a higher Levodopa content in the Brain, difficulty in movement has been seen with Sinemet at a lower dosage than preparations containing only L-Dopa. Other serious side effects are mental alterations, including tendencies towards paranoia and psychotic behavior, depression accompanied or not by suicidal tendencies, dementia. Convulsions are so rare as to not be considered directly relating to Sinemet. Another common but none the less unappealing side effect is nausea. Other less frequent side effects are cardia unevenness and/ or palpitations, cases of orthostatic, hypertension, bradykinesia (the on/ off phenomenon), anorexia, vomiting and vertigo. Rare cases have been reported of gastrointestinal hemorrhaging, duodenal ulcer, hypertension, phlebitis, leucopenia, agranulcytosis, Thrombocytopenia, hemolytic and non hemolytic anemia. Positive Comb's Tests have been carried out both with Sinemet and with Levodopa on it's own. Lab tests have shown the following abnormalities- - Alkaline phosphates, SGOT, SGPT, lactic- dehyrogenase, bilirubin, azotaemia, iodine left in protein. Other side effects described in conjunction with Levodopa are the following- - Psychiatric: Ataxia, fainting, increased trembling of the hands, muscular spasms, muscular cramp, trismus, activation of a latent hroner syndrome. Gastrointestinal- Constipation, diarrhea, abdominal pain and discomfort, meteorism, hiccups, excess flow of saliva, bitter taste in the mouth, dryness of the faeces, burning feeling in the tongue, dysphasia, teeth grinding. Dermatological- Hot flushes, increased and/ or dark perspiration, alopecia, skin eruptions. Urogenital- Urine retention, incontinence, dark urine, priapism, haematuria. Sense Organs- Blurred vision, diplopia, dilated pupils, oculogyric problems. Metabolism- Weight loss, oedema. Others- Weakness, listlessness, fatigue, headaches, hoarseness, uneasiness, nervousness, irregular breathing rate, malignant neuroleptic syndrome. In the Case of Overdose In the case of severe overdose, the treatment is basically the same as with severe overdose with treatment of Levodopa used alone. General first-aid measures should be carried out in addition to immediate gastric lavage. The application of liquid intravenously must be measured and air passages must be kept clear. Adequate electrocardiograph control should be carried out to permit the prompt detection of the development of the arrhythmia. The possibility that the patient may have taken another medication at the same time as Sinemet should be taken into account. As yet, there has been no research carried out regarding dialysis and thus it's possible application in the case of overdose is unknown. Vitamin B6 will not affect the action of Sinemet