Midodrine Hydrochloride

血液透析患者AVF内瘘狭窄及阻塞等并发症严重影响血管通路的功能和使用，致密的纤维化或增生组织使部分病变难以用普通压力的球囊完全扩张开，特别是对于顽固性狭窄及较长段的狭窄，是导致手术失败和通畅率低的主要原因。分析其原因可能与PTA 过程中球囊对内膜及部分中膜新生组织不规则的暴力撕裂，使内皮血管受损,血管平滑肌细胞、巨噬细胞发生剧烈增殖有关。近年来国际上不断有关于高压球囊、刻痕球囊、药涂球囊等用于透析通路PTA治疗的探索与临床研究，鼎科医疗专业从事血管介入医疗产品研发和生产，专注于球囊创新，研发了Dissolve™ AV刻痕药物球囊，集“高压”、“刻痕”和“药涂”于一体，针对性解决血透通路狭窄多项热点难点。 鼎科医疗特推出【柯城区人民医院-曹汉华教授：反复血栓形成的复杂动静脉内瘘头静脉弓狭窄的处理】病例展示，演绎每个病例的精细操作和先进器材器械的临床应用，从不同病例治疗策略的制定、术中规范化流程和技术应用、并发症预防、围手术期管理等方面，旨在推动血透通路狭窄诊疗规范化，加强医生们的技术交流和经验分享，以期为血透通路未来诊疗提供新思路和新方法，造福更多临床患者。 反复血栓形成的 复杂动静脉内瘘头静脉弓狭窄的处理 柯城区人民医院 曹汉华 基本信息  NO.1  患者：女，60岁。 主诉：血透12年，静脉压升高4天。 现病史：患者12年余前因诊断“多囊肾 慢性肾脏病5期 腹膜透析相关性腹膜炎”由腹膜透析改为血液透析治疗，血管通路为左上臂自体动静脉内瘘，透析频率为每周3次（周2；4；6），每次历时4小时，平素血透过程顺利。2023-6至2023-8患者多次因内瘘血栓形成于我院住院行手术治疗，末次手术为2023-8-21，行上肢静脉导管溶栓+导管吸栓+球囊扩张+静脉造影术，术程顺利，术后内瘘流量及静脉压可，血透过程顺利。4天前患者血透过程中静脉压升高最高280mmHg，血流量尚可，自诉触摸内瘘管壁较前僵硬明显，无左前臂肿胀，无疼痛，无肢端麻木不适，无畏寒发热，为进一步诊治，至我院就诊，门诊拟“慢性肾脏病5期、人工动静脉瘘狭窄”收住入院。 既往史：患者14年余前发现“多囊肾、多囊肝”，当时查血肌酐260umol/L，后因血肌酐进行性升高行透析治疗；14年余前发现“肾性高血压”，近2月因血压低服用米多君片升压治疗；否认外伤史，否认输血史，否认药物、食物过敏史。 查体：视诊：右上肢肘横纹上2cm处可见一长约2.5cm纵行手术瘢痕，头静脉迂曲明显，可见明显瘤样扩张，无皮损。触诊：双侧上肢皮温正常，内瘘吻合口及吻合口上方2cm处可扪及明显搏动，有微弱震颤。听诊：内瘘吻合口可闻及单向吹风样杂音。 入院诊断：术前诊断： 人工动静脉瘘狭窄； 多囊肾 慢性肾脏病5期 肾性贫血 肾性高血压 血液透析状态； 多囊肝。 血管通路病史  NO.2  时间 主要治疗经过 2023-06-15 左上臂头静脉弓狭窄闭塞再通+上肢静脉导管溶栓+5mm高压球囊扩张+头静脉弓重建术 2023-06-16 上肢静脉导管溶栓+切开取栓+头静脉弓重建术+6mm高压球囊扩张 2023-08-21 上肢静脉造影+上腔静脉造影+上肢静脉导管溶栓+导管吸栓+5mm高压球囊扩张 术前分析  NO.3  术前分析：患者头静脉弓病变，既往2次行头静脉弓重建+PTA治疗。最后一次手术治疗后仅维持两个月，再次扩张需改变治疗方式，从而改善治疗效果。本次考虑使用刻痕药物球囊治疗。 手术目标 主要目标：通过刻痕药物球囊PTA治疗增加血管内径； 次要目标：抑制血管内膜增生，提高内瘘通畅率。 手术策略/方案：DSA下上肢静脉、中心静脉造影+左头静脉、左锁骨下静脉狭窄狭窄球囊扩张术（Dissolve™ AV）。 手术过程  NO.4  穿刺上臂头静脉后，置入7F血管鞘，导丝通过头静脉迂曲段血管，经头静脉置入上腔静脉内，予以5mm高压球囊，18ATM扩张，维持时间2min，完成过后造影显示狭窄病变回弹。 成后造影显示狭窄病变改善，无造影剂外渗，最狭窄处直径3.6mm。 经导丝交换置入7mm高压球囊，于左头静脉-锁骨下静脉交汇处狭窄病变部位反复扩张，球囊难以完全张开，予以16ATM反复扩张2次扩张，维持时间2min。 成后造影显示狭窄病变改善，无造影剂外渗，最狭窄处直径4.19mm。 肝素盐水预冲准备好6mm×6cm刻痕药物球囊（鼎科 Dissolve™ AV）经导丝交换置入刻痕药物球囊（鼎科 Dissolve™ AV），22-26ATM扩张，维持时间2min30S。 完成后造影显示狭窄病变解除明显，最狭窄处直径4.28mm。 随访  NO.5  出院情况：术后内瘘震颤良好，未扪及异常搏动，术后透析顺利，上机透析流量260ml/min，静脉压98mmHg透析过程中未诉内瘘处疼痛。 病例总结  NO.6  病例特点：患者反复内瘘血栓形成，既往曾反复2次行PTA治疗，上次扩张维持时间小于2个月。 术前评估要点：术前充分评估患者内瘘血管内膜增生情况和血管钙化程度，制定合理手术方案。 手术策略/技术要点：既要充分扩张增生内膜，又要抑制术后内膜增生，同时还要处理钙化狭窄病变，刻痕药物球囊Dissolve™ AV是最佳选择，其具有高压+刻痕+药涂的优势。 器械特点/使用技巧： 术前球囊仅需要用生理盐水冲洗球囊导丝腔，建议勿浸泡球囊端，避免药物脱载； 不要取下涂层保护套管，将球囊沿着导丝尾端送至鞘口，直到卡住鞘口； 如充盈压力小于RBP前，病变已充分扩张，请保持压力2分钟使药物充分贴敷。如充盈压力达到RBP时，病变并未充分扩张，请依旧保持压力2分钟后，卸压并转动球囊约60°再次扩张至RBP，并保持压力1分钟。如病变残余狭窄或弹性回缩很重，可用超高压球囊或比Dissolve AV直径大1mm的高压球囊，进行后扩。 手术记录  NO.7  一、2023-06-15 左上臂头静脉弓狭窄闭塞再通+上肢静脉导管溶栓+5mm高压球囊扩张+头静脉弓重建术 患者取平卧位，术前彩超检查示上臂内瘘迂曲扩张吻合口至头静脉弓全程血栓，常规消毒铺巾后,在上臂中段内瘘扩张处朝向吻合口置入6F血管鞘，于血管超声引导0.35超滑导丝至肱动脉，延导丝置入波科5*40mm扩张球囊（波士顿科学 MUSTANG ）后撤出导丝于球囊分别注入尿激酶10万单位，于吻合口处上5厘米处朝向近心端置入6F血管鞘，于血管超声引导0.35超滑导丝，导丝至上臂中上段迂曲处不能通过，延导丝置入波科5*40mm扩张球囊（波士顿科学 MUSTANG ）后撤出导丝于球囊分别注入尿激酶10万单位后予球囊挤压血栓大部分溶解血流恢复予拔除上臂中段血管鞘5.0血管缝线缝合穿刺点，再次在上臂迂曲处向近心端置入6F血管鞘，于血管超声引导0.35超滑导丝，导丝至头静脉弓不能通过延导丝置入波科5*40mm扩张球囊（波士顿科学 MUSTANG ）后撤出导丝于球囊分别注入尿激酶10万单位后予球囊挤压血栓大部分溶解血流恢复，但头静脉弓闭塞段仍不能通过，再次予球囊配合导丝尝试通过头静脉弓狭窄段，更换0.14导丝仍不能通过，在0.35导丝尝试发生导丝嵌顿断裂残留头静脉弓处，头静脉弓血栓再次形成，告知患者家属后予行开放手术。 患者行臂丛神经麻醉，重新消毒铺巾，予上臂中段做一3厘米手术切口，游离头静脉长约2厘米，予橡皮条控制血流。予锁骨中段下1厘米处做一7厘米手术切口，钝性分离出头静脉弓，见头静脉弓迂曲扩张，汇入锁骨下静脉段长约3厘米狭窄，予狭窄处离断血管，取出完整0.35导丝头段5厘米，开放血流喷出长约10X0.8厘米血栓，彩超探查内瘘内无残留血栓，予波科5*40mm扩张球囊（波士顿科学 MUSTANG ）扩张近锁骨下静脉头静脉弓，扩张后修剪狭窄及瓣膜做一2厘米斜型切口予迂曲头静脉以7.0血管缝线行补片缝合，开放血流后内径约0.4厘米，彩超检查示血流通畅，彻底止血后依次拔除血管鞘及缝合切口，术毕。 二、2023-06-16上肢静脉导管溶栓+切开取栓+头静脉弓重建术+6mm高压球囊扩张 患者取平卧位，暴露左上肢，术前彩超检查示内瘘吻合口至头静脉弓全程血栓，常规消毒铺巾后,分离原上臂中段皮肤切口，暴露头静脉，纵行切开静脉0.5cm，给予血管钳取出血栓，开放血流，喷射出多枚细小血栓，7-0血管缝线缝合血管，同时分离原锁骨中段皮肤切口，暴露头静脉弓，于原缝合处离断血管，血管钳取出长段血栓，稀肝素水冲洗，探查近端血管通畅，修剪头静脉迂曲部分，予以7-0血管缝线吻合血管，开放血流后见远端内瘘再次血栓形成，头静脉肩部可见狭窄，切开上臂中段原血管缝线，再次血管钳取出血栓，并于上臂中段置入6F血管鞘，注入尿激酶10万单位后置入0.35超滑导丝，沿导丝予波科6*40mm扩张球囊（波士顿科学 MUSTANG ）挤压血栓，同时调整血管鞘方向，朝近端置入导丝，沿导丝置入波科6*40mm扩张球囊（波士顿科学 MUSTANG ）于肩部头静脉狭窄处，分别给予16-20ATM扩张三次，狭窄处由2mm扩张至4mm，拔出球囊，血流信号增强，锁骨中段头静脉处再次出血，考虑血管硬化管壁薄有关，再次予以7-0血管缝线缝合，彩超探查内瘘血流连续，未见明显血栓，震颤可及，拔出血管鞘，依次缝合上臂中段及锁骨中段皮下组织、皮肤，无菌敷贴包扎 三、2023-08-21上肢静脉造影+上腔静脉造影+上肢静脉导管溶栓+导管吸栓+5mm高压球囊扩张 患者取平卧位，常规消毒铺巾后，于左上臂头静脉近肩部为穿刺点，朝向远心端穿刺成功，予以静脉给予肝素预防性抗凝，并置入8Fr血管鞘，超声引导下调整导丝，并在球囊导管辅助下顺利通过上臂头静脉血栓，并成功经吻合口处，撤出导丝，经球囊局部血栓内注入尿激酶溶栓，局部按摩待血栓部分溶解软化后，经导丝交换置入并连接吸栓导管（先瑞达 Aco Stream）系统，超声引导下于血栓内开始反复抽吸血栓，吸出大部分穿刺点远心端血栓，近端管腔压力增加，后经上臂下段朝向近心端置入8Fr血管鞘，并经导丝尝试通过上臂中段迂曲管腔置入近心端血栓部位，反复尝试失败，后翻转近心侧鞘管朝向近心端，经鞘管置入导丝，在导丝辅助下置入吸栓导管，于头静脉弓闭塞处，自近心端向远心端吸出该段血栓，后经鞘管置入导丝及5*60mm球囊，并顺利通过头静脉弓闭塞病变处成功置入左锁骨下静脉内，逐步予以8-22ATM反复扩张后局部闭塞病变及汇合处锁骨下静脉，今扩张后管腔再通，血流部分恢复，后复查超声提示上臂中下段近吻合口区域仍存在部分血栓附着，后再次于头静脉中段朝向远心端置入8Fr血管鞘，经鞘管置入吸栓系统并予以吸栓，后血栓大部分吸出，并出现血栓脱落，漂流至头静脉弓处，再次经近心端鞘管置入吸栓系统吸栓及配合活检钳取栓处理后血栓去除，再次于头静脉弓处予以5*60mm球囊扩张，最长维持时间1分钟，完成后局部管腔再通，超声显示最小内径3mm，接鞘管造影显示上臂头静脉再通，头静脉弓再通，左锁骨下静脉、左无名静脉、上腔静脉通畅，上臂头静脉震颤明显，依次拔除球囊，导丝，5-0PROLENE线缝合穿刺点后拔除血管鞘，用品止血后敷料包扎，术毕。 专家介绍 曹汉华 教授 本病例术者 柯城区人民医院，副院长，肾病科主任，主任医师。 浙江省县级医院龙头学科学科带头人，浙江省医坛新秀，衢州市115人才，浙江省医师协会肾脏病分会委员，衢州市医学会肾脏病学分会委员，浙江省医学会风湿病分会青年委员。 擅长：肾脏病及风湿病等诊疗，在难治性肾病方面及疑难血管通路维护方面积累了丰富经验，在浙江省率先开展穿刺法腹膜透析管置入术，开展的疑难内瘘建 立、维护的技术处于浙江先进水平。 科室介绍 柯城区人民医院肾病科是浙江省县级医学龙头学科、浙江省重点临床专科建设项目、衢州市市域共建重点学科、浙大一院肾脏病中心重点协作科室、全国卫生产业企业管理协会血液透析通路建立与维护技术应用及推广单位、长三角血管通路联盟成员单位，建有多个省级专家工作站。科室拥有主任医师2人，副主任医师4名，主治医师4名，住院医师3名，浙江大学附属第一医院肾脏病中心林维勤教授、吴建永教授，浙江大学附属邵逸夫医院肾病中心李华教授定期来院坐诊、手术、业务指导。目前科室开放床位45张，血透机位83张，目前长期维持透析人数200余人，每年开展血管通路手术例数及透析次数均位于衢州地区前列，在浙西地区率先开展腹腔镜腹膜透析导管植入术，甲状旁腺切除加移植术，内瘘狭窄球囊扩张及支架置入手术、中心静脉狭窄病变介入手术等技术。 主要诊治的病种：慢性肾炎、肾病综合征、IgA肾病、糖尿病肾病、高血压肾病、多发性骨髓瘤相关性肾病、慢性肾功能衰竭、泌尿系感染、系统性红斑狼疮、类风湿性关节炎、干燥综合征、硬皮病、皮肌炎等。 主要开展的手术：肾活检术、临时血透管置入术、半永久性带涤纶套血透导管置入术、自体动静脉内瘘成形术、人工血管动静脉内瘘成形术、自体/人工血管动静脉内瘘取栓术、自体/人工血管动静脉内瘘球囊扩张及支架置入术、即穿型人工血管内瘘成型术、DSA下中心静脉病变介入治疗，腹膜透析导管置入术、甲状旁腺切除+种植等。年手术量600余台，位于浙江省各肾病专科前列。 主要医疗技术：早期肾脏病诊治、慢性肾病免疫抑制治疗、血液透析、血液滤过、终末期肾病相关并发症诊治、腹膜透析等。

– Analysis indicates treatment with TERLIVAZ plus albumin in adults with HRS with rapid reduction in kidney function1 can help improve kidney function with lower HRS treatment-related healthcare utilization costs2 – – Journal manuscript with full data results now published in the December issue of Advances in Therapy – DUBLIN, Dec. 21, 2023 /PRNewswire/ -- Mallinckrodt plc, a global specialty pharmaceutical company, recently announced the publication of findings from a cost analysis of TERLIVAZ® (terlipressin) for injection for adults with hepatorenal syndrome (HRS) with rapid reduction in kidney function.1,2 This analysis assessed the treatment-related cost per patient response with TERLIVAZ plus albumin from a U.S. hospital perspective.2 The manuscript was published in the December 2023 print issue of Advances in Therapy and is also available on the Advances in Therapy website. TERLIVAZ is the first and only FDA-approved product indicated to improve kidney function in adults with HRS with rapid reduction in kidney function,1 an acute and life-threatening condition requiring hospitalization.3 HRS involving rapid reduction in kidney function1 is estimated to affect more than 42,000 Americans annually and rates of HRS hospitalizations are increasing.4 Please see Limitation of Use and Important Safety Information, including Boxed Warning, below. The publication, titled "Treatment-Related Cost Analysis of Terlipressin for Adults with Hepatorenal Syndrome with Rapid Reduction in Kidney Function," used a decision analytic model to estimate the treatment-related cost associated with TERLIVAZ plus albumin and other non-FDA approved treatments, such as midodrine and octreotide plus albumin and norepinephrine plus albumin, for adult patients with HRS with rapid reduction in kidney function.1,2 HRS treatment-related utilization of healthcare resources from the U.S. hospital perspective, including the incremental cost of intensive care unit (ICU) bed, dialysis, pulse oximetry monitoring and adverse events, was estimated based on the level of response.2 HRS reversal (or complete response) was defined as a decrease in serum creatinine (SCr) from baseline to ≤ 1.5 mg/dL on treatment (up to 24 hours after the last treatment dose).2 "Continued research on the real-world clinical and economic impact of TERLIVAZ is critical to further our understanding of the relationship between HRS treatment choice and patient outcomes, and the related healthcare costs," said George Wan, Ph.D., M.P.H., Vice President, Evidence Generation & Data Sciences. "These findings suggest that TERLIVAZ may help to improve kidney function with lower ICU, dialysis, and other HRS treatment-related healthcare utilization costs when compared to other non-FDA approved treatments used in the U.S. hospital setting.2" Key Findings2: The cost per response of TERLIVAZ plus albumin was lower than midodrine and octreotide plus albumin ($85,315 vs. $467,794) and norepinephrine plus albumin ($81,614 vs. $139,324). Midodrine and octreotide plus albumin resulted in higher ICU- and dialysis-related costs (ICU: $9,039; dialysis: $8,266) vs. TERLIVAZ plus albumin (ICU: $6,712; dialysis: $5,073). Similarly, norepinephrine plus albumin resulted in higher ICU- and dialysis-related costs (ICU: $22,656; dialysis: $6,873) vs. TERLIVAZ plus albumin (ICU: $6,382; dialysis: $5,068). The HRS reversal rate for those treated with TERLIVAZ plus albumin was higher than those treated with midodrine and octreotide plus albumin (55.56%; n=15/27 vs. 4.76%; n=1/21), and those treated with norepinephrine plus albumin (55.64%; n=74/133 vs. 26.92%; n=35/130). For every two patients treated with TERLIVAZ plus albumin instead of midodrine and octreotide plus albumin, one additional patient was estimated to achieve HRS reversal. For every four patients treated with TERLIVAZ plus albumin instead of norepinephrine plus albumin, one additional patient was estimated to achieve HRS reversal. Collectively, these findings suggest that TERLIVAZ can be considered a cost-effective, value-based treatment option for appropriate patients with HRS with rapid reduction in kidney function.1,2 Limitations2: Efficacy, safety, and treatment-related adverse event data were sourced from published head-to-head randomized clinical trials, which may not be generalizable to the entire adult HRS population and differed from the adverse events in the FDA-approved TERLIVAZ label. Verified HRS reversal, the primary endpoint of the CONFIRM trial for TERLIVAZ (NCT02770716), was not used in this analysis. Several assumptions for the model were made, including the proportion of patients treated on the general floor with midodrine and octreotide plus albumin, and norepinephrine plus albumin. Cost data from public sources may be different from the actual costs of a hospital/institution and may not reflect discounts or rebates offered by manufacturers. The analysis focuses on the treatment-related cost of care over 14 days of the initial hospitalization and due to the short time horizon, other mid- and long-term benefits of HRS reversal post-initial hospitalization are not captured, including the reduced need for dialysis, kidney transplantation, and better outcomes post-liver transplantation. This study was funded by Mallinckrodt Pharmaceuticals. INDICATION AND LIMITATION OF USE TERLIVAZ® is indicated to improve kidney function in adults with hepatorenal syndrome with rapid reduction in kidney function. Patients with a serum creatinine >5 mg/dL are unlikely to experience benefit. IMPORTANT SAFETY INFORMATION WARNING: SERIOUS OR FATAL RESPIRATORY FAILURE TERLIVAZ may cause serious or fatal respiratory failure. Patients with volume overload or with acute-on-chronic liver failure (ACLF) Grade 3 are at increased risk. Assess oxygenation saturation (e.g., SpO2) before initiating TERLIVAZ. Do not initiate TERLIVAZ in patients experiencing hypoxia (e.g., SpO2 <90%) until oxygenation levels improve. Monitor patients for hypoxia using continuous pulse oximetry during treatment and discontinue TERLIVAZ if SpO2 decreases below 90%. Contraindications TERLIVAZ is contraindicated: In patients experiencing hypoxia or worsening respiratory symptoms. In patients with ongoing coronary, peripheral, or mesenteric ischemia. Warnings and Precautions Serious or Fatal Respiratory Failure: Obtain baseline oxygen saturation and do not initiate TERLIVAZ in hypoxic patients. Monitor patients for changes in respiratory status using continuous pulse oximetry and regular clinical assessments. Discontinue TERLIVAZ in patients experiencing hypoxia or increased respiratory symptoms. Manage intravascular volume overload by reducing or discontinuing the administration of albumin and/or other fluids and through judicious use of diuretics. Temporarily interrupt, reduce, or discontinue TERLIVAZ treatment until patient volume status improves. Avoid use in patients with ACLF Grade 3 because they are at significant risk for respiratory failure. Ineligibility for Liver Transplant: TERLIVAZ-related adverse reactions (respiratory failure, ischemia) may make a patient ineligible for liver transplantation, if listed. For patients with high prioritization for liver transplantation (e.g., MELD ≥35), the benefits of TERLIVAZ may not outweigh its risks. Ischemic Events: TERLIVAZ may cause cardiac, cerebrovascular, peripheral, or mesenteric ischemia. Avoid use of TERLIVAZ in patients with a history of severe cardiovascular conditions or cerebrovascular or ischemic disease. Discontinue TERLIVAZ in patients who experience signs or symptoms suggestive of ischemic adverse reactions. Embryo-Fetal Toxicity: TERLIVAZ may cause fetal harm when administered to a pregnant woman. If TERLIVAZ is used during pregnancy, the patient should be informed of the potential risk to the fetus. Adverse Reactions The most common adverse reactions (≥10%) include abdominal pain, nausea, respiratory failure, diarrhea, and dyspnea. Please click here to see full Prescribing Information, including Boxed Warning. About Hepatorenal Syndrome (HRS) Hepatorenal syndrome (HRS) involving rapid reduction in kidney function1 is an acute and life-threatening condition that occurs in people with advanced liver disease.3 HRS is classified into two distinct types – a rapidly progressive type that leads to acute renal failure where patients are typically hospitalized for their care and a more chronic type that progresses over weeks to months.3 HRS involving rapid reduction in kidney function1 is estimated to affect more than 42,000 Americans annually and rates of HRS hospitalizations are increasing.4 If left untreated, HRS with rapid reduction in kidney function1 has a median survival time of less than two weeks and greater than 80 percent mortality within three months.5 ABOUT MALLINCKRODT Mallinckrodt is a global business consisting of multiple wholly owned subsidiaries that develop, manufacture, market and distribute specialty pharmaceutical products and therapies. The company's Specialty Brands reportable segment's areas of focus include autoimmune and rare diseases in specialty areas like neurology, rheumatology, hepatology, nephrology, pulmonology, ophthalmology, and oncology; immunotherapy and neonatal respiratory critical care therapies; analgesics; cultured skin substitutes and gastrointestinal products. Its Specialty Generics reportable segment includes specialty generic drugs and active pharmaceutical ingredients. To learn more about Mallinckrodt, visit . CAUTIONARY STATEMENTS RELATED TO FORWARD-LOOKING STATEMENTS This release contains forward-looking statements, including with regard to TERLIVAZ®, its potential to improve health and treatment outcomes, and its potential impact on patients. The statements are based on assumptions about many important factors, including the following, which could cause actual results to differ materially from those in the forward-looking statements: the effects of Mallinckrodt's recent emergence from bankruptcy; satisfaction of, and compliance with, regulatory and other requirements; actions of regulatory bodies and other governmental authorities; changes in laws and regulations; issues with product quality, manufacturing or supply, or patient safety issues or adverse side effects or adverse reactions associated with TERLIVAZ; and other risks identified and described in more detail in the "Risk Factors" section of Mallinckrodt's most recent Annual Report on Form 10-K and other filings with the SEC, all of which are available on its website. The forward-looking statements made herein speak only as of the date hereof and Mallinckrodt does not assume any obligation to update or revise any forward-looking statement, whether as a result of new information, future events and developments or otherwise, except as required by law. CONTACT Media Inquiries Green Room Communications 954-816-6003 [email protected] Investor Relations Daniel J. Speciale Senior Vice President, Finance and Chief Financial Officer, Specialty Generics 314-654-3638 [email protected] Derek Belz Vice President, Investor Relations 314-654-3950 [email protected] Mallinckrodt, the "M" brand mark and the Mallinckrodt Pharmaceuticals logo are trademarks of a Mallinckrodt company. Other brands are trademarks of a Mallinckrodt company or their respective owners. ©2023 Mallinckrodt. US-2300825 12/23 References 1 TERLIVAZ® (terlipressin) for Injection. Prescribing Information. Mallinckrodt Hospital Products Inc. 2023. 2 Huang X, et al. Treatment-Related Cost Analysis of Terlipressin for Adults with Hepatorenal Syndrome with Rapid Reduction in Kidney Function. Adv Ther. 2023;40:5432–5446. 3 National Organization for Rare Disorders. Hepatorenal Syndrome. Available at: . Accessed December 2023. 4 Singh J, Dahiya DS, Kichloo A, Singh G, Khoshbin K, Shaka H. Hepatorenal Syndrome: A Nationwide Trend Analysis from 2008 to 2018. Annals of Med. 2021;53: 2018-2024. doi.org/10/1080/07853890 5 Flamm, S.L., Brown, K., Wadei, H.M., et al. The Current Management of Hepatorenal Syndrome–Acute Kidney Injury in the United States and the Potential of Terlipressin. Liver Transpl. 2021;27:1191-1202. . SOURCE Mallinckrodt plc