指示

TIVDAK is indicated for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy.

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

重要的安全信息

方框警告:眼毒性
TIVDAK caused changes in the corneal epithelium and conjunctiva resulting in changes in vision, 包括严重的视力丧失, 和角膜溃疡. Conduct an ophthalmic exam at baseline, 每次剂量前, 根据临床表现. Adhere to premedication and required eye care before, during, and after infusion. 保留TIVDAK直到改进和恢复, 减少剂量, 或永久停止, 根据严重程度.

警告和预防措施

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眼部不良反应 occurred in 60% of patients with cervical cancer treated with TIVDAK across clinical trials. 结膜不良反应最常见(40%), 干眼病(29%), 角膜不良反应(21%), 和睑缘炎(8%). 3例发生3级眼部不良反应.8%的患者,其中严重溃疡性角膜炎3例.2%的病人. One patient experienced ulcerative keratitis with perforation requiring corneal transplantation. Cases of symblepharon were reported in patients with other tumor types treated with TIVDAK at the recommended dose.

204年innovaTV, 4% of patients experienced visual acuity changes to 20/50 or worse including 1% of patients who experienced a visual acuity change to 20/200. Of the patients who experienced decreased visual acuity to 20/50 or worse, 75%的解决, including the patient who experienced decreased visual acuity to 20/200. 

Refer patients to an eye care provider for an ophthalmic exam including visual acuity and slit lamp exam at baseline, 每次剂量前, 根据临床表现. Adhere to premedication and required eye care to reduce the risk of ocular adverse reactions. Promptly refer patients to an eye care provider for any new or worsening ocular signs and symptoms. 保留剂量, 减少剂量, 或永久停止 TIVDAK based on the severity of the adverse reaction.

周围神经病变(PN) occurred in 42% of cervical cancer patients treated with TIVDAK across clinical trials; 8% of patients experienced Grade 3 PN. PN不良反应包括周围神经病变(20%), 周围感觉神经病(11%), 周围感觉运动神经病(5%), 运动神经病变(3%), 肌肉无力(3%), 脱髓鞘周围性多发性神经病变(1%). One patient with another tumor type treated with TIVDAK at the recommended dose developed Guillain- Barre syndrome. 监测病人神经病变的体征和症状. 对于新的或恶化的PN, 保留, 剂量减少, 或永久停止 TIVDAK based on the severity of PN.

出血 occurred in 62% of cervical cancer patients treated with TIVDAK across clinical trials. The most common all grade hemorrhage adverse reactions were epistaxis (44%), 血尿(10%), 阴道出血(10%). 5%的患者发生3级出血.

监测患者出血的体征和症状. For patients experiencing pulmonary or CNS hemorrhage, permanently discontinue TIVDAK. 其他部位出血≥2级, 直到出血消失, 血液血红蛋白稳定, there is no bleeding diathesis that could increase the risk of continuing therapy, and there is no anatomical or pathologic condition that can increase the risk of hemorrhage recurrence. After resolution, either resume treatment 或永久停止 TIVDAK.

肺炎: 严重的, 威胁生命的, or fatal 肺炎 can occur in patients treated with antibody-drug conjugates containing vedotin, 包括TIVDAK. Among patients with cervical cancer treated with TIVDAK across clinical trials, 2 patients (1.3%) experienced 肺炎, including 1 patient who had a fatal outcome.

监测患者肺炎的肺部症状. 传染性, 肿瘤, and other causes for symptoms should be excluded through appropriate investigations.

Withhold TIVDAK for patients who develop persistent or recurrent Grade 2 肺炎 and consider dose reduction. Permanently discontinue TIVDAK in all patients with Grade 3 or 4 肺炎.

Embyro-Fetal毒性: TIVDAK can cause fetal harm when administered to a pregnant woman. 告知患者胎儿的潜在危险. Advise females of reproductive potential to use effective contraception during treatment with TIVDAK and for 2 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with TIVDAK and for 4 months after the last dose.

不良反应

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Serious adverse reactions occurred in 43% of patients; the most common (≥3%) were ileus (6%), 出血(5%), 肺炎(4%), PN, 脓毒症, 便秘, 发热(各3%). Fatal adverse reactions occurred in 4% of patients who received TIVDAK, 包括感染性休克, 肺炎, 突然死亡, 多系统器官衰竭(各1%).

Adverse reactions leading to permanent discontinuation occurred in 13% of patients receiving TIVDAK; the most common (≥3%) were PN (5%) and corneal adverse reactions (4%). Adverse reactions leading to dose interruption occurred in 47% of patients; the most common (≥3%) were PN (8%), 结膜不良反应(4%), 和出血(4%). Adverse reactions leading to dose reduction occurred in 23% of patients; the most common (≥3%) were conjunctival adverse reactions (9%) and corneal adverse reactions (8%).

最常见的不良反应(≥25%), 包括实验室异常, 血红蛋白降低(52%), 疲劳(50%), 淋巴细胞减少(42%), 恶心(41%), PN (39%), 脱发(39%), 鼻出血(39%), 结膜不良反应(37%), 出血(32%), 白细胞减少(30%), 肌酐增加(29%), 干眼病(29%), 凝血酶原国际标准化比值增加(26%), 部分凝血活酶激活时间延长(26%), 腹泻(25%), 和皮疹(25%).

药物的相互作用

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强大的CYP3A4抑制剂: Concomitant use with strong CYP3A4 inhibitors may increase unconjugated monomethyl auristatin E (MMAE) exposure, 哪些可能增加TIVDAK不良反应的风险. 密切监测患者TIVDAK不良反应.

适用于特定人群

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中度或重度肝损害: MMAE暴露和不良反应增加. 避免使用.

哺乳期: Advise lactating women not to breastfeed during TIVDAK treatment and for at least 3 weeks after the last dose.

Please see full Prescribing Information, including BOXED WARNING.
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