英文药名: Visudyne(Verteporfin injection) 中文药名: 维替泊芬注射剂 生产厂家: 诺华制药 ビスダイン静注用15mg 治疗类别名称 年龄相关性黄斑变性的治疗剂（对于配方光动力疗法） 商標名 Visudyne 構造式 下記の２種の位置異性体（I、II）の１:１混合物 一般名 ベルテポルフィン（Verteporfin） 化学名 A 1：1 mixture of(4RS,4aSR)-4,4a-dihydro-3,4-methoxycarbonyl-9-(2-methoxycarbonylethyl)-4a,8,14,19-tetramethyl-18-vinyl-23H,25H-benzo[b]porphine-13-propionic acid and(4RS,4aSR)-4,4a-dihydro-3,4-methoxycarbonyl-13-(2-methoxycarbonylethyl)-4a,8,14,19-tetramethyl-18-vinyl-23H,25H-benzo[b]porphine-9-propionic acid 分子式 C41H42N4O8 分子量 718.79 性状 深绿色，黑色固体。N，N-二甲基甲酰胺，以更可溶，难溶在四氢呋喃中，在乙醇（99.5）微溶，在乙腈极微溶于，和几乎不溶于水。 熔点 244〜258℃ 条件批准 接受这种药物用于光动力治疗的培训，充分了解与此相关的药物使用的安全性和有效性，准备这种药物，给药，只能用激光足够的知识和经验，对光线照射的医生通过使用，采取必要的措施的事情。 药效药理 作用机序 该PDT由两个步骤的过程中，有必要通过静脉内输注和眼科的光动力学治疗激光器维替泊芬（无热原二极管激光器）两个处理的光照射。维替泊芬是通过在血浆中的低密度脂蛋白（LDL）主要输送，结合到LDL-受体内皮细胞。维替泊芬某种程度上选择性积聚在新生血管（包括CNV）。 被光活化的氧维替泊芬的存在的高反应性是在CNV，会出现短暂的活性氧自由基和单线态氧。由激活接收由CNV新生血管内皮维替泊芬局部损坏的光，其结果是，发生血管闭塞。 通过脂氧合酶途径和环氧合酶途径，解放了促凝血因子和血管活性剂，血小板聚集受损内皮，可导致纤维蛋白凝块（纤维化像素块）的形成和血管收缩被确认。因为组织如CNV已经在LDL-受体的增加，维替泊芬是相对选择性的CNV积累，在动物模型中已经表明，维替泊芬也存在于视网膜上。 因此，存在的附带损害即使光活化的视网膜结构，包括视网膜色素上皮细胞或视网膜外颗粒层发生的可能性。该CNV闭塞发生维替泊芬治疗后，已经由人类的荧光眼底造影证实。 适应症 适用于继发于年龄相关性黄斑变性，病理性近视或可疑眼组织胞浆菌病的，以典型性为主型中心凹下脉络膜新生血管形成的患者。对于隐匿性中心凹下脉络膜新生血管为主的患者，尚无充分证据支持治疗。 用法用量 治疗分为两个步骤，同时需要药物和激光。第一步静脉输注维替泊芬，第二步用非热性二极管激光活化维替泊芬。每隔3 个月医生需要检查患者，一旦荧光血管造影出现脉络膜新生血管渗漏就应该重复治疗。病灶大小判定病灶最大线性距离（GLD）通过荧光血管造影和彩色眼底像判定。各种典型和隐匿型CNV，出血和/或荧光遮挡，任何视网膜色素上皮浆液性脱离都应该进行判定。建议使用2.4~2.6 倍的彩色眼底照相机。荧光血管造影片上病灶的GLD 必须经过相机放大率矫正，获得病灶在视网膜上的GLD。光斑大小判定治疗光斑大小应该比病灶在视网膜上GLD 大1000um，留有500um 的边缘，保证完全覆盖病灶。 临床研究应用的最大治疗光斑为6400um。治疗光斑的鼻侧缘必须距离视乳头颞侧至少200um，即使这样会在视神经200um范围内出现CNV 光凝不足。 包装规格 静脉注射 15毫克*1瓶 生产和销售（进口） 诺华制药有限公司 完整处方资料附件： 1）：http://product.novartis.co.jp/vis/ 2）：http://www.info.pmda.go.jp/go/pack/1319401F1026_2_11/ Therapeutic category name Age-related macular degeneration treatment agent (Photodynamic therapy for the formulation) Brand Name Visudyne intravenous 15mg composition Component-content 1 vial verteporfin 15mg Additive Lactose 690mg Egg phosphatidylglycerol 48.75mg Dimyristoyl phosphatidylcholine 70.50mg Palmitic acid, ascorbic acid 0.15mg Dibutylhydroxytoluene 0.015mg Contraindication There is a possibility that exacerbate of porphyria patients [symptoms] Patients with a history of hypersensitivity to components of this drug In patients such as the fundus of the observation is that there is a strong cataract or corneal opacity of the degree of difficulty of the patient [turbid, it is difficult to the fundus of the observation, also, appropriate light irradiation amount of energy to the lesion of interest whether you want to reach because it is unknown, it is impossible to enforce adequate treatment with this drug] Efficacy or effect Age-related macular degeneration with subfoveal choroidal neovascularization In patients with Occult CNV (choroidal neovascularization) or minimally classic CNV, the effectiveness of this drug (visual loss suppression) because there is a performance of the was no statistically significant difference with placebo, this in these patients It is judged on that took into consideration the risks and benefits for applying the agent. (See the section of the CLINICAL STUDIES]) 6mg/m2 (the body surface area) was administered intravenously over 10 minutes as verteporfin, laser light in the 15 minutes after the administration of this drug beginning [wavelength 689 ± 3nm, in the light irradiation amount of energy 50J/cm2 (irradiation output 600mW/cm2 83 seconds)] is irradiated to the treatment spot. In addition, fluorescein leakage from choroidal neovascularization in fluorescence angiography during inspection of every three months If it is admitted, to implement the re-treatment. Photodynamic therapy with this drug (this PDT), the intravenous administration activation of Visudyne by laser light irradiation from the (first stage) and ophthalmic photodynamic therapy laser (non-pyrogenic diode laser) of this drug consisting of (stage 2) two processes. It was dissolved by adding to this agent 1 vial a day stations water for injection 7mL, to prepare a solution of 7.5mL containing verteporfin 2mg/mL. Aspirated Visudyne solution of 6 mg / m2 (body surface area) or equivalent amount from the vial, diluted with as Japanese Pharmacopoeia Dextrose Injection to become 30mL total amount (5%), and administration for injection solutions. The total amount of 30mL using the appropriate syringe pump and infusion-line filter, for 10minutes (3mL/min) over a period of administering intravenously. If the extravasation of the drug was observed, immediately discontinue administration, performs a cold compress, since there is a possibility that the severe local photosensitivity reaction (sunburn, etc.) is expressed, swelling and discoloration withdrawal to fully protect the site of leakage from direct sunlight until. Since this drug is to be precipitated with saline solution, solution other than the day stations water for injection (physiological saline solution, etc.) that you do not use. Further, it is not performed co-injection with other agents. Dissolution, after dilution in the dark until use, to be used within 4 hours. Standard considerations of this drug in the administration to avoid extravasation Check the intravenous line before starting the intravenous administration of this drug, be carefully monitored after administration. Since the elderly are more likely the vein wall is vulnerable, vein of as large as possible the arm, it is desirable to use the elbow vein before, if possible. Administration from a thin vein of the back of the hands is avoided. Measurement of lesion size The maximum diameter of the lesion by fluorescein angiography and color fundus photograph (GLD: greatest linear dimension) to measure. All of the classic CNV and occult CNV, blood or fluorescence of the block (blocked fluorescence) and the inclusion of serous detachment of the retinal pigment epithelium in this measurement. In addition, the fundus camera is within the scope of the magnification 2.4 to 2.6 is desirable. For GLD of the lesion on fluorescein angiography, by adding a correction for magnification of the fundus camera, to calculate the GLD of retinal lesions. Determination of spot size Treatment spot size, do the edging of 500μm to retinal lesion, in order to ensure that the lesion can be completely covered, add 1,000μm to GLD. However, nasal edge of the treatment spot, a position away more than 200μm from the side head side edge of the optic disc. [To avoid damage to the optic nerve should be avoided laser irradiation within 200μm from the optic. In patients with lesions are present in very close to the optic nerve, because you can not completely cover the lesion, does not cause light activation of the CNV within 200μm from the optic nerve, the effectiveness of this drug may be reduced] Laser light irradiation In the case of patients who are using the vision correction contact lenses, to start treatment from remove contact lenses prior to the present PDT. Activation by light of verteporfin to control the total amount of energy to be irradiated. Irradiation amount of energy in the CNV of treatment is 50J per CNV lesion 1cm2 (at an irradiation output 600mW / cm2 will be illuminated 83 seconds). Appropriately to illuminate the laser beam to pre-determined treatment spot, the amount of irradiation energy, irradiation output, the magnification of the ophthalmic lens, the setting of the zoom lens becomes an important parameter. In accordance with laser system manual to be used is about setting up and operation of the laser irradiation procedure, to strictly comply with the irradiation conditions as defined in usage and dosage. 689 to use a laser that can output to stabilize the wavelength of ± 3nm. Laser light using a suitable ophthalmic magnifying lens, to irradiate the retina as a single circle spot via an optical fiber and slit lamp. If necessary, it can be used in combination retrobulbar anesthesia to prevent eye movement. Binocular therapy (both eyes treated in clinical trials have not been performed.) Avoid both eyes co-treatment in the initial treatment. Incidentally, if there is a lesion to be treated in both eyes, it is necessary to carefully evaluate the benefits and risks of both eyes simultaneously treated. There is no experience who underwent this PDT in the past, for patients with lesions to be treated in both eyes, first one eye underwent only this PDT to (lesions eye is in progress), was observed more than a week above, in particular only if it can be determined that there is no safety problem, taking into account the implementation of the PDT to the other eye. To enforce this PDT against one eye in the past, in the case where there is no particular safety problems, for patients with lesions to be treated in both eyes, the first to the progress of the eye is a more advanced lesions as the target, that the enforcement of this PDT in accordance with usage and dose. Then immediately re-set the laser for the treatment of other eye, within 20 minutes from the administration of this drug started (the end of the administration within 10 minutes) to the light irradiation to. Careful administration Patients with obstructive liver failure or bile duct [metabolism or excretion is likely to be delayed] More than 10 times of high doses of the recommended clinical dose to the patient[atropine and sedated pigs or anesthesia pig with ketamine under anesthesia (2mg/kg) in the test was administered rapidly intravenously, the results and ideas of complement activation severe circulatory failure have been observed, including the death to be. These effects are diminished or lost by the administration prior to the antihistamine. In addition, these effects are not seen in the absence of anesthesia pig, no anesthesia, not observed in dogs regardless of the under general anesthesia] [In in vitro studies using human blood, complement activation of mild to moderate was observed at a concentration of 10μg/mL (concentration of more than 5 times the expected maximum blood concentration of this drug-treated patients), 100μg/ concentration of greater than or equal to mL at a significant complement activation has been observed. Complement activation that are clinically meaningful in clinical studies have not been reported, but can not eliminate the risk of anaphylactic reaction expressed by complement activation] Clinical results for patients [the patient of retinal vascular growth tumor (Retinal Angiomatous Proliferation) rather than, efficacy and safety has not been established] Rather than clinical outcomes for patients [the patient that merger retinopathy, including diabetic retinopathy, efficacy and safety has not been established] Clinically significant adverse reactions Because there is that side effects such as the following may occur. Patients should be carefully observed, if the symptoms are observed, discontinue administration and take appropriate measures. Eye disorder Severe vision loss (3.1%), abnormal vision (metamorphopsia, blurred vision, etc.) (4.7%), visual field defect (frequency unknown), vitreous hemorrhage (frequency unknown), subretinal hemorrhage (1.6%), retinal peeling (frequency unknown), retinal pigment epithelial detachment (frequency unknown), retinal pigment epithelium hiatus (frequency unknown) Anaphylactoid reaction, vasovagal reaction (incidence unknown) Fainting, sweating, dizziness, rash, dyspnea, flushing, changes in blood pressure, may be accompanied by a general condition such as a change in heart rate. Cerebral infarction (1.6%), aortic aneurysm (1.6%), myocardial infarction (1.6%) Hemorrhagic gastric ulcer (frequency unknown) Systemic pain (frequency unknown) Pharmacology Mechanism of action The PDT is composed of a two-step process, it is necessary to both treatment of the light irradiation by intravenous infusion and ophthalmic photodynamic therapy lasers verteporfin (apyrogenic diode laser). Verteporfin is transported primarily by the low density lipoprotein (LDL) in plasma, bind to the LDL-Receptor endothelial cells. Verteporfin to some extent selectively accumulates in the nascent blood vessels (including the CNV). High reactivity to be activated by light in the presence of oxygen verteporfin is in CNV, reactive oxygen radicals and singlet oxygen of the short-lived occurs. New by the activation by light of verteporfin in the CNV Raw vascular endothelium undergo locally damaged, as a result, vascular occlusion occurs. Damaged endothelium via the lipoxygenase pathway and the cyclooxygenase pathway, liberated procoagulant factors and vasoactive agents, platelet aggregation, can lead to fibrin clot (fibrosis pixel block) formation and vasoconstriction are confirmed. Because the tissues such as CNV has been an increase in the LDL-receptor, verteporfin is relatively selectively accumulate in CNV, in animal models have shown that verteporfin is also present in the retina. Accordingly, there is a possibility that collateral damage even after light activation in the retina structure including retinal pigment epithelium or retina external granular layer occurs. After Visudyne therapy that CNV occlusion occurs, it has been confirmed by fluorescent fundus angiography of the human.