近日，美国食品和药物管理局(FDA)批准Dsuvia的申请。Dsuvia适用于成人急性疼痛的治疗，严重到需要在医院、外科中心和急诊科等经医学监督的医疗机构使用阿片类镇痛药。
AcelRx联合创始人兼首席医疗官帕梅拉·帕尔默(Pamela Palmer)说:“FDA批准Dsuvia是近15年研究的成果，该研究旨在提高在医疗监督下治疗急性疼痛的护理标准。”“作为一名麻醉师，我看到了静脉注射阿片类药物给患者和提供者带来的挑战，比如静脉注射的延迟，静脉注射的困难，以及注射阿片类药物的药物错误。”AcelRx成立的目的是开发一种简单、有效、无创的止痛剂，使医护人员能够快速处理病人的急性疼痛。
批准日期：2018年11月2日 公司：AcelRx制药公司
DSUVIA(舒芬太尼[sufentanil])舌下片,供口服使用, CII
美国初步批准:2018年
警告:意外暴露和DSUVIA REMSPROGRAM;危及生命的呼吸抑制;成瘾、滥用和滥用;细胞色素P450 3 a4interaction;以及伴随使用而产生的风险
苯二氮平类药物或其他中枢神经抑制剂
请参阅完整的盒装警告说明。
•意外接触或摄入DSUVIA，尤其是儿童，可导致呼吸抑制和死亡。由于意外暴露有危及生命的呼吸抑制风险，DSUVIA只能通过一个名为DSUVIA REMS的受限项目获得(参见警告和预防措施)。DSUVIA应仅由经过认证的医疗监督的医疗保健机构的卫生保健提供者管理。停止使用dsuvia之前，从认证医疗监督设置出院或转移。
•可能发生严重、危及生命或致命的呼吸抑制。密切监视，特别是在启动过程中。
•DSUVIA暴露给使用者阿片类药物成瘾、滥用和滥用的风险，这可能导致过量和死亡。在开处方前评估病人的风险，并定期监测这些行为和状况。
•伴随使用CYP3A4抑制剂(或停止使用CYP3A4诱导剂)可导致致命剂量的舒芬太尼。
•与苯二氮平类药物或其他中枢神经系统(中枢神经系统)镇静剂(包括酒精)同时使用阿片类药物，可能导致深度镇静、呼吸抑制、昏迷和死亡。为不适合其他治疗方案的病人开处方;将剂量和使用期限限制在规定的最低限度;并跟踪患者呼吸抑制和镇静的体征和症状。
作用机制
舒芬太尼是一种阿片激动剂，对阿片受体具有相对选择性，尽管它可以在较高剂量下与其他阿片受体结合。舒芬太尼的主要治疗作用是镇痛和镇静，被认为是通过阿片类特异性受体介导的整个中枢神经系统。像所有的全阿片激动剂一样，镇痛没有天花板效应。
适应症和用法
DSUVIA含有舒芬太尼(一种阿片类激动剂)，适用于成人在经认证的医疗监督的医疗环境中，如医院，外科中心和急诊科，用于治疗严重到需要阿片类镇痛药的急性疼痛
治疗是不够的。
使用的局限性
•不用于家庭使用或儿童使用。在病人离开认证的医疗监督医疗机构之前，停止使用DSUVIA进行治疗。
•使用时间不超过72小时。
•仅由医疗保健提供者管理。
•由于阿片类药物存在成瘾、滥用和误用的风险，即使是推荐剂量，也要保留DSUVIA以供患者选择其他治疗方案。非阿片类镇痛药或阿片类药物组合产品]:
-没有被容忍，或不被期望被容忍，
-没有提供足够的镇痛，或预期没有提供等同的镇痛。
剂量和管理
•推荐剂量为30微克/次，每次最少1小时。
•24小时内不要超过12片。
•查看管理信息的完整处方信息。
•不要在身体依赖的病人中突然中断DSUVIA。
剂型及强度
•舌下片:30微克片，置于一次性单剂量片(SDA)中。
禁忌症
严重的呼吸抑制[见警告和注意事项]
•在未经监控的环境下或在没有复苏设备的情况下发生急性或严重支气管哮喘。
•已知或疑似胃肠道阻塞，包括麻痹性肠梗阻。
•已知对舒芬太尼或DSUVIA成分过敏。
警告和预防措施
•慢性肺部疾病患者或老年人、恶病质患者或虚弱患者危及生命的呼吸抑制:密切监测，特别是在起始和滴定期间。
•5 -羟色胺综合征:伴随5 -羟色胺能药物治疗可能导致潜在的生命危险。怀疑是5 -羟色胺综合症。
•肾上腺功能不全:如果诊断出来，就用皮质类固醇的生理性替代治疗，并使患者戒除阿片类药物。
•严重低血压:监测剂量起始和滴定过程。循环休克患者避免使用DSUVIA。
•使用颅内压增高、脑肿瘤、头部损伤或意识受损患者的风险:监测镇静和呼吸抑制。避免在意识受损或昏迷的病人中使用DSUVIA。
不良反应
最常报道的不良反应(≥2%)恶心、头痛、呕吐、头晕、低血压。
要报告可疑的不良反应，请联系AcelRxPharmaceuticals, inc(1-855-925-8476)或FDA (1-800-FDA-1088或www.fda.gov/medwatch)。
药物的相互作用
•混合激动剂/拮抗剂和部分激动剂阿片类镇痛药:避免使用DSUVIA，因为它们可能会降低DSUVIA的镇痛效果或导致患者突然戒断症状。
用于特定人群
•肝和/或肾损害:监测镇静和呼吸抑制的迹象。
包装提供/存储和处理
提供
每片DSUVIA片剂30微克装在单剂量点药器(SDA)中，包装在一个捣固明显的箔袋内。分发版有一个介绍:
•NDC 61621-430-11(每箱10袋)
在使用DSUVIA后，应将SDA处理在生物危害废物中。
指示卫生保健提供者采取措施安全储存DSUVIA，并按照机构CII程序处理掉的、放错位置的DSUVIA药片。
储存和处理
储存在室温下DSUVIA 20-25ºC,远足允许15 - 30ºC在安全,访问位置有限,为人民共和国产品依照制度程序。
完整说明书附件：http://dsuvia.com/shared/pdf/PL-6410_FINAL__110218.pdf
DSUVIA(sufentanil)sublingual tablet 30 mcg
IMPORTANT SAFETY INFOMATION
WARNING: ACCIDENTAL EXPOSURE AND DSUVIA REMS PROGRAM; LIFE-THREATENING RESPIRATORY DEPRESSION; ADDICTION, ABUSE, AND MISUSE; CYTOCHROME P450 3A4 INTERACTION; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS
Accidental Exposure and DSUVIA Risk eva luation and Mitigation Strategy (REMS) Program
Accidental exposure to or ingestion of DSUVIA, especially in children, can result in respiratory depression and death. Because of the potential for life-threatening respiratory depression due to accidental exposure, DSUVIA is only available through a restricted program called the DSUVIA REMS Program.
DSUVIA must only be dispensed to patients in a certified medically supervised healthcare setting.
Discontinue use of DSUVIA prior to discharge or transfer from the certified medically supervised healthcare setting.
Life-Threatening Respiratory Depression
Serious, life-threatening, or fatal respiratory depression may occur with use of DSUVIA. Monitor for respiratory depression, especially during initiation of DSUVIA.
Addiction, Abuse, and Misuse
DSUVIA exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient’s risk prior to prescribing DSUVIA, and monitor all patients regularly for the development of these behaviors or conditions.
Cytochrome P450 3A4 Interaction
The concomitant use of DSUVIA with all cytochrome P450 3A4 inhibitors may result in an increase in sufentanil plasma concentrations, which could increase or prolong adverse drug reactions and may cause potentially fatal respiratory depression. In addition, discontinuation of a concomitantly used cytochrome P450 3A4 inducer may result in an increase in sufentanil plasma concentration. Monitor patients receiving DSUVIA and any CYP3A4 inhibitor or inducer.
Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants
Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death.
Reserve concomitant prescribing 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.
Indications and Usage
DSUVIA is indicated for use in adults in a certified medically supervised healthcare setting, such as hospitals, surgical centers, and emergency departments, for the management of acute pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate.
Limitations of Use:
Not for home use or for use in children. Discontinue treatment with DSUVIA before patients leave the certified medically supervised healthcare setting.
Not for use for more than 72 hours. The use of DSUVIA beyond 72 hours has not been studied.
Only to be administered by a healthcare provider.
Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, reserve DSUVIA for use in patients for whom alternative treatment options [e.g., non-opioid analgesics or opioid combination products]:
Have not been tolerated, or are not expected to be tolerated,
Have not provided adequate analgesia, or are not expected to provide adequate analgesia.
Contraindications
Use of DSUVIA is contraindicated in patients with:
Significant respiratory depression
Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment
Known or suspected gastrointestinal obstruction, including paralytic ileus
Known hypersensitivity to sufentanil or components of DSUVIA.
Warnings and Precautions
Accidental ingestion or exposure to even one dose of DSUVIA, especially in children, can result in respiratory depression and death due to an overdose of sufentanil.
DSUVIA is for use in adult patients only in a certified medically supervised healthcare setting. Use of DSUVIA outside of this setting can increase the risk of accidental exposure in others for whom it is not prescribed, causing fatal respiratory depression. Discontinue use of DSUVIA prior to discharge or transfer from the certified medically supervised healthcare setting. DSUVIA is not for home or pediatric use.
DSUVIA contains sufentanil, a Schedule II controlled substance. As an opioid, DSUVIA exposes users to the risks of addiction, abuse, and misuse.
Profound sedation, respiratory depression, coma, and death may result from the concomitant use of DSUVIA with benzodiazepines or other CNS depressants (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol). Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.
Life-threatening respiratory depression in patients with chronic pulmonary disease or in elderly, cachectic and debilitated patients: monitor patients closely, particularly when initiating DSUVIA therapy and when DSUVIA is used with other drugs that depress respiration. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient’s clinical status.
A potentially life-threatening condition could result from concomitant serotonergic drug administration. Discontinue DSUVIA if serotonin syndrome is suspected. Cases of adrenal insufficiency have been reported with opioid use (usually > 1 month). Presentation and symptoms are non-specific and include nausea, vomiting, anorexia, fatigue, weakness, dizziness and low blood pressure. Confirm diagnosis with testing as soon as possible and, if confirmed, treat with physiologic replacement of corticosteroids and wean patient from opioid.
As with all opioids, sufentanil may produce bradycardia or hypotension in some patients. Therefore DSUVIA should be used with caution in patients with bradyarrhythmias or hypovolemia.
DSUVIA should not be used in patients who may be particularly susceptible to the intracranial effects of CO2 retention, such as those with evidence of increased intracranial pressure, impaired consciousness or coma.
Prolonged use of DSUVIA during pregnancy can result in withdrawal in the neonate, which can be life-threatening. Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly. Advise pregnant women using opioids for a prolonged period of this risk and ensure that appropriate treatment will be available.
Insufficient data are available on the use of DSUVIA in patients with severe liver or kidney impairment. DSUVIA should be used with caution in such patients due to the importance of these organs in the metabolism and excretion of sufentanil.
Adverse Reactions
Adverse reactions are described, or described in greater detail, in other sections of the Prescribing Information:
Life-Threatening Respiratory Depression [see Warnings and Precautions (5.3)]
Addiction, Abuse, and Misuse [see Warnings and Precautions (5.4)]
Adrenal Insufficiency [see Warnings and Precautions (5.9)]
Severe hypotension [see Warnings and Precautions (5.10)]
Gastrointestinal Adverse Reactions [see Warnings and Precautions (5.12)]
Seizures [see Warnings and Precautions (5.13)]
Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions (5.15)]
The most commonly reported adverse reactions (≥ 2% and higher than placebo) were nausea, headache, vomiting, dizziness, and hypotension.
Medical Information
For medical inquiries or to report an adverse event, other safety-related information or product complaints for a company product, please contact the AcelRx Medical Information Contact Center at 1-855-925-8476 or AcelRxMedInfo@rmpdc.org.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.