近日，美国食品和药物管理局（FDA）已批准鼻腔喷雾剂Valtoco（diazepam）上市。Valtoco是第一个也是唯一一个被批准用于6岁及以上癫痫患者癫痫丛集发作抢救性治疗的鼻腔喷雾剂。
VALTOCO（diazepam）鼻腔喷雾剂是地西泮的专有制剂，通过鼻腔喷雾剂给药，开发用于治疗癫痫发作活动增加（也称为急性反复性或丛集性癫痫发作）的六岁及以上癫痫患者。
批准日期：2020年1月13日 公司：Neurelis，Inc
VALTOCO（地西泮[diazepam]）鼻喷雾剂，CIV
美国最初批准：1963年
警告：与以下产品同时使用有风险
阿片类药物查看完整的处方信息，以获取完整的框内警告。并用苯二氮卓类药物和阿片类药物可能会导致严重的镇静，呼吸抑制，昏迷和死亡。
作用机理
地西泮的确切作用机理尚不完全清楚，但据认为涉及增强GABA能神经传递，这是由于在GABAA受体的苯二氮卓部位结合引起的。
适应症和用途
VALTOCO是一种苯二氮卓类药物，用于急性治疗频繁发作的间歇性刻板发作（即癫痫发作，急性重复性发作），与6岁及以上癫痫患者的常规发作方式不同。
剂量和给药
仅通过鼻腔途径管理VALTOCO。
剂量取决于患者的年龄和体重。
初始剂量：VALTOCO 5mg和10mg剂量作为一次鼻内喷雾剂喷入一个鼻孔。15毫克和20毫克剂量的给药需要两个鼻喷雾器，每个鼻孔喷雾一次。
第二次剂量：如果需要，可以在初始剂量后至少4小时给予第二次剂量。如果使用，请使用新的泡罩包装。
最大剂量和治疗频率：单次治疗不要使用超过2剂剂量。建议VALTOCO应每5天不超过1次治疗，每月不超过5次。
剂量形式和强度
鼻喷雾剂：0.1mL，5mg，7.5mg或10mg地西泮。
禁忌症
•对地西泮过敏。
•急性窄角型青光眼。
警告和注意事项
•中枢神经系统抑制：与酒精或其他中枢神经系统抑制药合用时，可能会导致中枢神经系统抑制作用增强。
•自杀行为和观念：抗癫痫药会增加自杀观念和行为的风险。
不良反应
最常见的不良反应（至少4％）是嗜睡，头痛和鼻腔不适。
要报告可疑的不良反应，请与Neurelis，Inc。联系。请致电1-866-696-3873或FDA请致电1-800-FDA-1088或www.fda.gov/medwatch。
药物相互作用
•CYP2C19和CYP3A4抑制剂：与VALTOCO的不良反应可能增加。
•CYP2C19和CYP3A4诱导剂：VALTOCO给药后地西epa的暴露量可能减少。
在特定人口中使用
•怀孕：根据动物数据，可能会造成胎儿伤害。
包装供应/存储和处理方式
供应方式
VALTOCO有5毫克，7.5毫克和10毫克浓度。供应和包装VALTOCO的剂量分别为5mg，10mg，15mg或20mg（见表4）。
表4：可用的包装配置
规格                      内容                                     NDC
5毫克   2个独立的泡罩包装，每个泡罩包装包含一个5mg鼻喷雾器      72252-505-02
10毫克  2个独立的泡罩包装，每个泡罩包装包含一个10毫克的鼻喷雾器 72252-510-02
15毫克  2个独立的泡罩包装，每个泡罩包装包含两个7.5 mg鼻喷雾器   72252-515-04
20毫克  2个独立的泡罩包装，每个泡罩包装包含两个10mg鼻喷剂       72252-520-04
储存和处理
使用前，请勿打开单独的泡罩包装或测试鼻喷雾器。
每个单剂量鼻腔喷雾装置只能喷雾一（1）次，并且不能重复使用。
如果鼻喷雾器看起来已损坏，请不要使用。
将VALTOCO存放在20o
C至25o C（68o F至77o F）; 允许的温度偏移范围是15°C至30°C（59°F至86°F）[请参阅USP控制的室温]。不要冻结。避光。
完整资料附件：
https://www.valtoco.com/sites/default/files/VALTOCO_Prescribing_Information.pdf
FDA Approval for Seizure Rescue Treatment VALTOCO(Diazepam Nasal Spray)that Incorporates the Science of Intravail® for Consistent and Reliable Absorption
U.S. Food and Drug Administration(FDA)has approved VALTOCO(diazepam nasal spray)as an acute treatment of intermittent, stereotypic episodes of frequent seizure activity (i.e., seizure clusters, acute repetitive seizures) that are distinct from a patient's usual seizure pattern in people with epilepsy 6 years of age and older.The unique formulation of VALTOCO incorporates Intravail®for consistent and reliable absorption.
Indication
VALTOCO(diazepam nasal spray)is indicated for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity(ie, seizure clusters, acute repetitive seizures) that are distinct from a patient's usual seizure pattern in patients with epilepsy 6 years of age and older.
IMPORTANT SAFETY INFORMATION
RISK FROM CONCOMITANT USE WITH OPIOIDS
Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death.
Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate
Limit dosages and durations to the minimum required
Follow patients for signs and symptoms of respiratory depression and sedation
Contraindications: VALTOCO is contraindicated in patients with:
Known hypersensitivity to diazepam
Acute narrow-angle glaucoma
Central Nervous System(CNS)Depression
Benzodiazepines, including VALTOCO, may produce CNS depression. Caution patients against engaging in hazardous activities requiring mental alertness, such as operating machinery, driving a motor vehicle, or riding a bicycle, until the effects of the drug, such as drowsiness, have subsided, and as their medical condition permits.The potential for a synergistic CNS-depressant effect when VALTOCO is used with alcohol or other CNS depressants must be considered, and appropriate recommendations made to the patient and/or care partner.
Suicidal Behavior and Ideation
Antiepileptic drugs(AEDs), including VALTOCO, increase the risk of suicidal ideation and behavior.Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or unusual changes in mood or behavior. Advise patients and caregivers to be alert for these behavioral changes and to immediately report them to a healthcare provider.
Glaucoma
Benzodiazepines, including VALTOCO, can increase intraocular pressure in patients with glaucoma. VALTOCO may only be used in patients with open-angle glaucoma only if they are receiving appropriate therapy.VALTOCO is contraindicated in patients with narrow-angle glaucoma.
Risk of Serious Adverse Reactions in Infants due to Benzyl Alcohol Preservative
VALTOCO is not approved for use in neonates or infants. Serious and fatal adverse reactions, including "gasping syndrome," can occur in neonates and low-birth-weight infants treated with benzyl alcohol-preserved drugs, including VALTOCO. The "gasping syndrome" is characterized by central nervous system depression, metabolic acidosis, and gasping respirations. The minimum amount of benzyl alcohol at which serious adverse reactions may occur is not known.