美国FDA批准Fetzima（levomilnacipran）缓释胶囊为第四款新药治疗成人重性抑郁 批准日期：2016年1月  公司：阿特维斯制药 FETZIMA（左旋米那普仑 levomilnacipran）缓释胶囊，口服使用 最初美国批准：2009 警告： 自杀的想法和行为，请参阅完整的黑框警告完整的处方信息。 增加了儿童，青少年和年轻成年人自杀想法和行为的风险服用抗抑郁药。 监测恶化，自杀念头和行为的出现。 FETZIMA没有被批准用于儿科患者使用。 目前的主要变化 禁忌-移除不受控制的窄角型青光眼  07/2014 警告和注意事项-闭角型青光眼   07/2014 作用机理 levomilnacipran的抗抑郁作用的确切机理还不清楚，但被认为是在中枢神经系统中与血清素和去甲肾上腺素的增强，通过再摄取的抑制在血清素和去甲肾上腺素转运。非临床研究显示，levomilnacipran是一种强效和选择性血清素和去甲肾上腺素再摄取抑制剂（SNRI）。 适应症和用法 FETZIMA是血清素和去甲肾上腺素再摄取抑制剂（SNRI），用于重度抑郁症（MDD）的的治疗来表示。 使用限制：FETZIMA没有被批准用于纤维肌痛的管理。对于纤维肌痛症的管理的疗效和FETZIMA的安全尚未建立。 用法用量 推荐剂量： 40毫克至120毫克，每天一次或没有食物。 20毫克，每天一次2天开始剂量，然后每天一次提高到40毫克。 根据有效性和耐受性，增加的40毫克的增量剂量以2或更多天的时间间隔。 最大推荐剂量为120毫克，每天一次。 以胶囊的整体;不开，咀嚼或咬碎 肾损害：不要为中度受损，每天一次超过80毫克。不要为严重肾功能不全，每天一次超过40毫克。 中止：逐步减少剂量尽可能 剂型和规格 缓释胶囊：20毫克，40毫克，80毫克和120毫克。 禁忌症 过敏levomilnacipran，米那普仑盐酸，或在FETZIMA制剂的任何赋形剂。 羟色胺综合征和单胺氧化抑制剂：不要使用单胺氧化抑制剂用于治疗与FETZIMA或在7天内与FETZIMA停止治疗的精神障碍。不要在停车用来治疗精神疾病的单胺氧化酶的14天内使用FETZIMA。此外，不要在谁是被利奈唑胺或静脉注射亚甲蓝治疗的患者开始FETZIMA。 警告和注意事项 自杀的想法和行为的儿童，青少年和年轻成人：监测患者的临床恶化，自杀想法或行为。 血清素综合征血清素综合症已报道的SSRIs和SNRIs的，既当单独存在时，尤其是当共同给予与其他血清素药物（包括曲坦类药物，三环，芬太尼，锂，曲马多，色氨酸，丁螺环酮和圣约翰草）。如果出现这样的症状，请停止FETZIMA并开始支持治疗。如与其他药物血清素的FETZIMA同时使用在临床上合理的，患者应该知道血清素综合征的潜在风险增加，尤其是在治疗开始和增加剂量。 血压升高和心率：在开始治疗前和定期整个处理措施心脏速率和血压。预控原有高血压开始治疗与FETZIMA之前。 异常出血：治疗可以增加出血的危险。警告患者中约的出血与使用的NSAIDs，阿司匹林，或影响凝血其它药物相关的风险。 闭角型青光眼：闭角型青光眼发生的患者与抗抑郁药处理未处理的解剖窄房角。 尿犹豫或保留：可发生。如果出现这些症状，应停止FETZIMA或考虑以其他适当医疗干预。 疯狂/轻躁狂的激活：屏幕患者躁郁症，戒约躁狂/轻躁狂的活化风险的患者。 发作：可发生。请小心使用患者的癫痫症。 停药综合征：锥剂量时可能和监控停药症状。 低钠血症：可发生于协会SIADH。 不良反应 最常见的不良反应（发生率≥5％和安慰剂的至少两倍的速率）为：恶心，便秘，多汗症，心脏速率增加，勃起功能障碍，心动过速，呕吐，和心悸。 要报告疑似不良反应，请联系森林制药公司在1-800-678-1605或FDA电话1-800-FDA-1088或www.fda.gov/medwatch。 药物相互作用 强CYP3A4抑制剂如酮康唑：不要每天一次超过80毫克。 特殊人群中使用 妊娠：根据动物实验数据，可能会对胎儿造成伤害。 FETZIMA(levomilnacipran extended-release capsules) FETZIMA INDICATION AND USAGE FETZIMA (levomilnacipran extended-release capsules) is a serotonin and norepinephrine reuptake inhibitor (SNRI) indicated for the treatment of Major Depressive Disorder (MDD) in adults. FETZIMA is not approved for the management of fibromyalgia, and its efficacy and safety have not been established for that use. IMPORTANT SAFETY INFORMATION WARNING: SUICIDAL THOUGHTS AND BEHAVIORS Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term studies. These studies did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in patients over age 24; there was a reduction in risk with antidepressant use in patients aged 65 and older. In patients of all ages who are started on antidepressant therapy, monitor closely for worsening, and for emergence of suicidal thoughts and behaviors. Advise families and caregivers of the need for close observation and communication with the prescriber. FETZIMA is not approved for use in pediatric patients. Contraindications •FETZIMA is contraindicated in patients with a hypersensitivity to levomilnacipran, milnacipran HCl, or to any excipient in the formulation. •The use of MAOIs intended to treat psychiatric disorders with FETZIMA or within 7 days of stopping treatment with FETZIMA is contraindicated due to an increased risk of serotonin syndrome. The use of FETZIMA within 14 days of stopping an MAOI intended to treat psychiatric disorders is also contraindicated. Starting FETZIMA in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue is also contraindicated due to an increased risk of serotonin syndrome. Warnings and Precautions •All patients being treated with antidepressants should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the first few months of treatment and when increasing or decreasing the dose. Consider changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse or includes symptoms of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, mania, or suicidality that are severe, abrupt in onset, or were not part of the patient's presenting symptoms. Families and caregivers of patients being treated with antidepressants should be alerted about the need to monitor patients daily. Prescriptions for FETZIMA should be written for the smallest quantity of capsules consistent with good patient management, in order to reduce the risk of overdose. •Serotonin Syndrome: The development of a potentially life-threatening serotonin syndrome has been reported with SNRIs and SSRIs both when taken alone, but especially when co-administered with other serotonergic agents (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John’s Wort) and with drugs that impair metabolism of serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue). Symptoms of serotonin syndrome may include mental status changes (eg, agitation, hallucinations, delirium, and coma), autonomic instability (eg, tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (eg, tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms. If symptoms of serotonin syndrome occur, discontinue FETZIMA immediately and initiate supportive treatment. If concomitant use of FETZIMA with other serotonergic drugs is clinically warranted, patients should be aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases. •SNRIs, including FETZIMA, have been associated with increases in blood pressure. Blood pressure should be measured prior to initiating treatment and periodically throughout FETZIMA treatment. Pre-existing hypertension should be controlled before initiating treatment with FETZIMA. Use with caution in patients with pre-existing hypertension, cardiovascular, or cerebrovascular conditions that might be compromised by increases in blood pressure. Concomitant use of FETZIMA with drugs that increase blood pressure and heart rate has not been evaluated and such combinations should be used with caution. For patients who experience a sustained increase in blood pressure, discontinuation or other appropriate medical intervention should be considered. •SNRIs, including FETZIMA, have been associated with an increase in heart rate. Heart rate should be measured prior to initiating treatment and periodically throughout FETZIMA treatment. Pre-existing tachyarrhythmias and other cardiac disease should be treated before starting therapy with FETZIMA. For patients who experience a sustained increase in heart rate, discontinuation or other appropriate medical intervention should be considered. •SSRIs and SNRIs, including FETZIMA, may increase the risk of bleeding events, some serious. Concomitant use of aspirin, NSAIDs, warfarin, and other anticoagulants may add to this risk. •Angle closure glaucoma has occurred in patients with untreated anatomically narrow angles treated with antidepressants. The pupillary dilation that occurs following use of many antidepressant drugs including FETZIMA may trigger an angle closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy. •FETZIMA can affect urethral resistance. In clinical studies, urinary hesitation occurred in 4%, 5% and 6% of FETZIMA-treated patients receiving doses of 40, 80, and 120 mg, respectively, compared to no patients in the placebo group. Caution is advised when using FETZIMA in patients prone to obstructive urinary disorders. •Symptoms of mania/hypomania were reported in 0.2% of FETZIMA-treated patients and 0.2% of placebo-treated patients in clinical studies. As with all antidepressants, FETZIMA should be used cautiously in patients with a history or family history of bipolar disorder, mania or hypomania. Prior to initiating treatment with FETZIMA, patients should be adequately screened to determine if they are at risk for bipolar disorder. FETZIMA is not approved for use in treating bipolar depression. •FETZIMA should be prescribed with caution in patients with a seizure disorder. •Discontinuation symptoms, some serious, have been reported with discontinuation of serotonergic antidepressants such as FETZIMA. Gradual dose reduction is recommended, instead of abrupt discontinuation, whenever possible. Monitor patients when discontinuing FETZIMA. If intolerable symptoms occur following a dose decrease or upon discontinuation of treatment, consider resuming the previously prescribed dose and decreasing the dose at a more gradual rate. •Advise patients that if they are treated with diuretics or are otherwise volume depleted, or are elderly, they may be at greater risk of developing hyponatremia while taking FETZIMA. Although no cases of hyponatremia resulting from FETZIMA treatment were reported in the clinical studies, hyponatremia has occurred as a result of treatment with SSRIs and SNRIs. FETZIMA should be discontinued in patients with symptomatic hyponatremia and appropriate medical intervention should be instituted. Adverse Reactions The most commonly observed adverse reactions in MDD patients treated with FETZIMA in placebo-controlled studies (incidence ≥5% and at least twice the rate of placebo) were: nausea (17% vs 6%), constipation (9% vs 3%), hyperhidrosis (9% vs 2%), heart rate increased (6% vs 1%), erectile dysfunction (6% vs 1%), tachycardia (6% vs 2%), vomiting (5% vs 1%), and palpitations (5% vs 1%). FETZIMA Rx Pharmacological Class: Serotonin and norepinephrine reuptake inhibitor (SNRI). Active Ingredient(s): Levomilnacipran 20mg, 40mg, 80mg, 120mg; ext-rel caps. Company Forest Laboratories Indication(s): Treatment of major depressive disorder (MDD) in adults. Limitations of use: not approved for the management of fibromyalgia. The efficacy and safety for the management of fibromyalgia have not been established. Pharmacology: Although the exact mechanism of the antidepressant action of levomilnacipran is unknown, it is thought to be related to the potentiation of serotonin and norepinephrine in the CNS, through inhibition of reuptake at serotonin and norepinephrine transporters. Clinical Trials: The efficacy of Fetzima was established in three 8-week, randomized, double-blind, placebo-controlled studies at doses 40–120mg once daily in adult outpatients with MDD. Two of these studies were fixed dose (Study 1 and Study 2), and one study was flexible dose (Study 3). In Study 1 (N=713), patients received Fetzima 40mg, 80mg, or 120mg once daily or placebo. In Study 2 (N=562), patients received either Fetzima 40mg or 80mg once daily or placebo. In Study 3 (N=434), patients received Fetzima 40–120mg once daily or placebo. In all three studies, Fetzima demonstrated superiority over placebo in the improvement of depressive symptoms, as measured by the Montgomery-Asberg Depression Rating Scale (MADRS) total score. Fetzima also demonstrated superiority over ­placebo as measured by ­improvement in the Sheehan Disability Scale functional impairment total score. For more clinical trial results, see full labeling. Legal Classification: Rx Adults: Swallow whole. Initially 20mg once daily for 2 days, and then increase to 40mg once daily; may increase dose in 40mg increments at intervals of ≥2 days; max 120mg once daily. Renal impairment: moderate (CrCl 30–59mL/min): max 80mg once daily; severe (CrCl 15–29mL/min): max 40mg once daily. ESRD: not recommended. Concomitant strong CYP3A4 inhibitors: max 80mg once daily. Children: <18years: not established. Contraindication(s): During or within 14 days of MAOIs. Concomitant linezolid or IV methylene blue (see full labeling). Uncontrolled narrow-angle glaucoma. Warnings/Precautions: Increased risk of suicidal thinking and behavior in children, adolescents, and young adults; monitor closely for clinical worsening and unusual changes. Monitor for serotonin syndrome; discontinue if develops. History of bipolar disorder, mania, or hypomania. Pre-existing hypertension, cardio- or cerebrovascular disease, or tachyarrhythmias. Monitor BP and heart rate; reduce dose or discontinue if elevation persists. Risk of bleeding. Controlled narrow-angle glaucoma. Obstructive urinary disorders. Seizure disorder. Volume depleted. Hyponatremia risk (esp. in elderly). Reevaluate periodically. Write Rx for smallest practical amount. Avoid abrupt cessation. Pregnancy (Category C). Nursing mothers: not studied. Interaction(s) See Contraindications. Allow at least 14 days after MAOI discontinuation before starting levomilnacipran; allow at least 7 days after discontinuing levomilnacipran before starting an MAOI. Increased risk of serotonin syndrome with other serotonergic drugs (eg, triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, St. John's Wort) or with drugs that impair serotonin metabolism (eg, MAOIs, linezolid, IV methylene blue). Increased risk of bleeding with concomitant NSAIDs, aspirin, anticoagulants; monitor. Concomitant strong CYP3A4 inhibitors (eg, ketoconazole, clarithromycin, ritonavir): adjust dose. Avoid alcohol. Caution with other CNS-active drugs, or drugs that can increase BP or heart rate. Adverse Reaction(s) Nausea, constipation, vomiting, hyperhidrosis, increased heart rate, erectile dysfunction, tachycardia, palpitations; hypertension, urinary hesitation. How Supplied: Caps 20mg—30; 40mg, 80mg, 120mg—30, 90 Titration Pack—1 (2 x 20mg + 26 x 40mg)