BOXED WARNING: SERIOUS SKIN REACTIONS

  • PADCEV可引起严重和致命的皮肤不良反应,包括Stevens-Johnson综合征(SJS)和中毒性表皮坏死松解(TEN), which occurred predominantly during the first cycle of treatment, 但以后可能会发生.
  • 关闭ly monitor patients for skin reactions.
  • 立即停用PADCEV,并考虑转诊到专科治疗怀疑SJS或10或严重的皮肤反应.
  • Permanently discontinue PADCEV in patients with confirmed SJS or TEN; or Grade 4 or recurrent Grade 3 skin reactions.

指示

PADCEV®适用于成人局部晚期或转移性尿路上皮癌(mUC)患者的治疗:

  • 是否曾接受程序化死亡受体1 (PD-1)或程序化死亡配体1 (PD-L1)抑制剂和含铂化疗, or
  • 是否不适合使用含顺铂的化疗,且之前曾接受过一种或多种治疗方案.

重要的安全信息

警告和预防措施

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皮肤反应: 严重皮肤不良反应, including fatal cases of SJS or TEN, occurred in patients 对待PADCEV. SJS and TEN occurred predominantly during the first cycle of treatment 但以后可能会发生. Skin reactions occurred in 55% of the 680 patients 对待PADCEV in clinical trials. Twenty-three percent (23%) of patients had maculo-papular rash and 33% had 瘙痒. Grade 3-4 skin reactions occurred in 13% of patients, 包括maculo-papular皮疹, 皮疹的红斑, 皮疹或药疹, symmetrical drug-related intertriginous and flexural exanthema (SDRIFE), 皮炎大泡的, 皮炎表皮剥脱的, and palmar-plantar erythrodysesthesia. 在临床试验中, the median time to onset of severe skin reactions was 0.6个月(范围:0.1 to 6.4). 发生皮肤反应导致剂量中断,然后重新启动PADCEV的患者(n=59), 24%的患者以相同剂量重新开始治疗,16%的患者以减少剂量重新开始治疗,出现复发性严重皮肤反应. Skin reactions led to discontinuation of PADCEV in 2.6%的病人. Monitor patients closely throughout treatment for skin reactions. Consider topical corticosteroids and antihistamines, as clinically indicated. 拒绝使用PADCEV,并将疑似SJS或TEN或严重(3级)皮肤反应转到专科治疗. Permanently discontinue PADCEV in patients with confirmed SJS or TEN, or for Grade 4 or recurrent Grade 3 skin reactions.

Hyperglycemia and diabetic ketoacidosis (DKA), 包括致命的事件, occurred in patients with and without pre-existing diabetes mellitus, 对待PADCEV. Patients with baseline hemoglobin A1C ≥8% were excluded from clinical trials. 在临床试验中, 14% of the 680 patients 对待PADCEV developed hyperglycemia; 7% of patients developed Grade 3-4 hyperglycemia. 在高体重指数和高基线A1C的患者中,3-4级高血糖的发生率持续增加. 5%的患者需要胰岛素治疗来治疗高血糖. The median time to onset of hyperglycemia was 0.6个月(范围:0.1 to 20.3). Hyperglycemia led to discontinuation of PADCEV in 0.6%的病人. 关闭ly monitor blood glucose levels in patients with, 或有患, 糖尿病或高血糖. If blood glucose is elevated (>250 mg/dL), withhold PADCEV.

肺炎 Severe, life-threatening or fatal pneumonitis occurred in patients 对待PADCEV. 在临床试验中,3.1% of the 680 patients 对待PADCEV had pneumonitis of any grade and 0.7%有3-4年级. 在临床试验中, the median time to onset of pneumonitis was 2.9个月(范围:0.6 to 6). Monitor patients for signs and symptoms indicative of pneumonitis, 如缺氧, 咳嗽, dyspnea or interstitial infiltrates on radiologic exams. 评估并排除传染性, 通过适当的调查发现肿瘤和其他引起这些症状的原因. 拒绝对持续或复发的2级肺炎患者使用PADCEV,并考虑减少剂量. Permanently discontinue PADCEV in all patients with Grade 3 or 4 pneumonitis.

周围神经病变(PN) occurred in 52% of the 680 patients 对待PADCEV in clinical trials, including 39% with sensory neuropathy, 7% with muscular weakness and 6% with motor neuropathy; 4% experienced Grade 3-4 reactions. PN occurred in patients 对待PADCEV with or without pre- existing PN. The median time to onset of Grade ≥2 PN was 4.6个月(范围:0.1 to 15.8个月). Neuropathy led to treatment discontinuation in 5% of patients. 监测患者新发或恶化的周围神经病变症状,并考虑在PN发生时中断或减少PADCEV的剂量. Permanently discontinue PADCEV in patients who develop Grade ≥3 PN.

眼部疾病 在计划进行眼科检查的临床试验中,384例使用PADCEV治疗的患者中,有40%的患者报告. 这些事件的大部分涉及角膜,包括干眼症相关的事件,如角膜炎, 视力模糊, 增加了流泪, 结膜炎, 角膜缘干细胞缺乏, 和角膜病. Dry eye symptoms occurred in 34% of patients, and 视力模糊 occurred in 13% of patients, 在使用PADCEV治疗期间. The median time to onset to symptomatic ocular disorder was 1.6个月(范围:0 ~ 19.1个月). Monitor patients for ocular disorders. 考虑使用人工泪液预防干眼症,并在眼部症状出现或未消除时进行眼科评估. Consider treatment with ophthalmic topical steroids, if indicated after an ophthalmic exam. Consider dose interruption or dose reduction of PADCEV for symptomatic ocular disorders.

网站输液外渗 观察PADCEV给药后皮肤和软组织的次生反应. 在680名患者中,1名.6%的病人 experienced skin and soft tissue reactions, including 0.3% who experienced Grade 3-4 reactions. 反应可能会延迟. 红斑, 肿胀, 增加温度, 外渗后2 ~ 7天疼痛加重,1 ~ 4周疼痛消退. 两个病人(0.3%) developed extravasation reactions with secondary cellulitis, bullae, or exfoliation. 在启动PADCEV之前,确保足够的静脉通路,并在给药期间监测可能的外渗. If extravasation occurs, stop the infusion and monitor for adverse reactions.

Embryo-fetal毒性 PADCEV can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to the fetus. 建议有生育潜力的女性患者在PADCEV治疗期间和最后一次剂量后2个月使用有效的避孕措施. 建议有生育潜力的女性伴侣的男性患者在使用PADCEV治疗期间和最后一次剂量后4个月使用有效的避孕措施.

不良反应

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Most Common 不良反应, Including Laboratory Abnormalities (≥20%)

皮疹, aspartate aminotransferase (AST) increased, 葡萄糖的增加, 肌酐增加, 乏力, PN, 淋巴细胞减少, 脱发, 食欲下降, 血红蛋白降低, 腹泻, 减少钠, 恶心想吐, 瘙痒, 磷酸下降, 味觉障碍, alanine aminotransferase (ALT) increased, 贫血, 白蛋白减少, 中性粒细胞减少, 尿酸盐增加, 脂肪酶的增加, 血小板减少, 体重减轻,皮肤干燥.

EV-301研究:296例患者曾接受PD-1/L1抑制剂和铂基化疗.

Serious adverse reactions occurred in 47% of patients 对待PADCEV; the most common (≥2%) were urinary tract infection, acute kidney injury (7% each) and pneumonia (5%). Fatal adverse reactions occurred in 3% of patients, including multiorgan dysfunction (1.0%), hepatic dysfunction, septic shock, hyperglycemia, pneumonitis and pelvic abscess (0.3%). Adverse reactions leading to discontinuation occurred in 17% of patients; the most common (≥2%) were PN (5%) and rash (4%). Adverse reactions leading to dose interruption occurred in 61% of patients; the most common (≥4%) were PN (23%), 皮疹(11%)和疲劳(9%). Adverse reactions leading to dose reduction occurred in 34% of patients; the most common (≥2%) were PN (10%), 皮疹(8%), 食欲下降 and 乏力 (3%). Clinically relevant adverse reactions (<15%) include vomiting (14%), AST增加(12%), 高血糖(10%), ALT增加(9%), pneumonitis (3%) and infusion site extravasation (0.7%).

EV-201, 队列2研究:89例既往接受PD-1/L1抑制剂治疗的患者,不符合铂基化疗的条件.

Serious adverse reactions occurred in 39% of patients 对待PADCEV; the most common (≥3%) were pneumonia, 败血症和腹泻(各5%). Fatal adverse reactions occurred in 8% of patients, including acute kidney injury (2.2%), metabolic acidosis, sepsis, multiorgan dysfunction, pneumonia and pneumonitis (1.1%). Adverse reactions leading to discontinuation occurred in 20% of patients; the most common (≥2%) was PN (7%). Adverse reactions leading to dose interruption occurred in 60% of patients; the most common (≥3%) were PN (19%), 皮疹(9%), 疲劳(8%), 腹泻(5%), AST increased and hyperglycemia (3%). Adverse reactions leading to dose reduction occurred in 49% of patients; the most common (≥3%) were PN (19%), 皮疹(11%)和疲劳(7%). Clinically relevant adverse reactions (<15%) include vomiting (13%), AST增加(12%), 脂肪酶的增加(11%), ALT增加(10%), pneumonitis (4%) and infusion site extravasation (1%).

药物的相互作用

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其他药物对PADCEV的影响 (Dual P-gp and Strong CYP3A4 Inhibitors)
同时使用双P-gp和强CYP3A4抑制剂可能增加未结合的单甲基auristatin E暴露, which may increase the incidence or severity of PADCEV toxicities. 当PADCEV与双P-gp和强CYP3A4抑制剂同时给予时,密切监测患者的毒性迹象.

特定的人群

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泌乳 建议哺乳期妇女在使用PADCEV治疗期间不要母乳喂养,并在最后一次剂量后至少3周.

肝损伤 Avoid the use of PADCEV in patients with moderate or severe hepatic impairment.

完整的你.S. Prescribing Information, including BOXED WARNING for Serious Skin Reactions.
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