Mesenteric Ischemia

– Oral presentation of a post hoc analysis of the Phase 3 CONFIRM trial details the therapeutic effect of TERLIVAZ in adult patients with hepatorenal syndrome (HRS) and alcoholic hepatitis (AH)1 – DUBLIN, Jan. 22, 2024 /PRNewswire/ -- Mallinckrodt plc, a global specialty pharmaceutical company, today announced the presentation of findings from a post hoc analysis of the Phase 3 CONFIRM clinical trial. In this analysis, treatment with TERLIVAZ® (terlipressin) for injection was associated with improvements in verified hepatorenal syndrome (HRS) reversal and HRS reversal vs. placebo in adult cirrhosis patients with alcoholic hepatitis (AH) and HRS with rapid reduction in kidney function.1,2 The results will be shared in an oral presentation at the Society of Critical Care Medicine (SCCM) 2024 Critical Care Congress, taking place January 21-23, 2024, in Phoenix, AZ. TERLIVAZ is the first and only FDA-approved product indicated to improve kidney function in adults with HRS with rapid reduction in kidney function,2 an acute and life-threatening condition requiring hospitalization.3 HRS involving rapid reduction in kidney function2 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 post hoc analysis evaluated the efficacy of TERLIVAZ in a subgroup of patients from the CONFIRM trial with HRS, acute-on-chronic liver failure (ACLF) grade 0–2 and serum creatinine (SCr) <5 mg/dL.1 The incidence of verified HRS reversal – defined as two consecutive SCr values ≤1.5 mg/dL at least two hours apart while on treatment and alive without renal replacement therapy (RRT) for at least 10 days – and HRS reversal – defined as SCr ≤1.5 mg/dL while on treatment – were assessed.1 "We are pleased to share the latest data providing valuable insight into the relationship between TERLIVAZ treatment and rates of verified HRS reversal in adult cirrhosis patients with AH compounded by HRS," said Peter Richardson, MRCP (UK), Executive Vice President & Chief Scientific Officer. "This research is a reflection of our commitment to provide healthcare providers with the most up-to-date clinical information to support critically ill patients, especially those with AH, and drive the importance of early recognition and treatment of HRS at lower SCr levels and ACLF grades for potentially better outcomes." A total of 117 patients in the subgroup analysis (N=300) met the criteria for evaluation (TERLIVAZ n=78; placebo n=39).1 The analysis found that the incidence of verified HRS reversal was significantly higher in patients treated with TERLIVAZ vs. placebo (TERLIVAZ: 32%, n=25; placebo: 8%, n=3: p=0.004), as well as the incidence of HRS reversal (TERLIVAZ: 37%, n=29; placebo: 10.3%, n=4: p=0.002).1 This study was sponsored by Mallinckrodt Pharmaceuticals. Presentation details can be found below: Abstract #1311: Terlipressin Improves Outcomes in Patients with HRS and Alcoholic Hepatitis: The CONFIRM Study1 Presenter: Jody C. Olson, MD, FACP, Department of Internal Medicine, Mayo Clinic, Rochester, MN Presentation Date: Monday, January 22, 2024; 2:30 – 3:30 p.m. MT Location: Connections Central – RST 04 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 function2 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 function2 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 function2 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; 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, its potential impact on patients, and the planned presentation regarding the TERLIVAZ trial. 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. ©2024 Mallinckrodt. US-2300993 01/24 References 1 Olson JC, et al. Terlipressin Improves Outcomes in Patients with HRS and Alcoholic Hepatitis: The CONFIRM Study. Oral presentation to be shared at the Society of Critical Care Medicine (SCCM) 2024 Critical Care Congress. January 2024. 2 TERLIVAZ® (terlipressin) for Injection. Prescribing Information. Mallinckrodt Hospital Products Inc. 2023. 3 National Organization for Rare Disorders. Hepatorenal Syndrome. Available at: . Accessed January 2024. 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;53:1. 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. doi.org/10.1002/lt.26072. SOURCE Mallinckrodt plc

– 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

– A total of 11 scientific abstracts from Mallinckrodt's research for adults with HRS with rapid reduction in kidney function1 provide further insight into the clinical efficacy, safety, and real-world utility of TERLIVAZ treatment for appropriate patients – – Mallinckrodt's presence to include three oral presentations and one AASLD Poster of Distinction – DUBLIN, Nov. 8, 2023 /PRNewswire/ -- Mallinckrodt plc (OTCMKTS: MNKTQ), a global specialty pharmaceutical company, today announced the presentation of 11 scientific abstracts with findings from the latest clinical and health economics research with TERLIVAZ® (terlipressin) for injection for adult patients with hepatorenal syndrome (HRS) with rapid reduction in kidney function1 during the American Association for the Study of Liver Diseases (AASLD) 2023 Liver Meeting, taking place November 10-14, 2023 in Boston, MA. Continue Reading Video Showcasing Mallinckrodt Presence at AASLD View PDF HRS Infographic Experience the interactive Multichannel News Release here: Included among Mallinckrodt's breadth of data for adults with HRS with rapid reduction in kidney function1 are three oral presentations and one Poster of Distinction detailing research of clinical outcomes with TERLIVAZ2,3,4 and real-world health economics outcomes for TERLIVAZ-treated patients with comorbidities.5 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.6 HRS involving rapid reduction in kidney function1 is estimated to affect more than 35,000 Americans annually and rates of HRS hospitalizations are increasing.7,8 Please see Limitation of Use and Important Safety Information, including Boxed Warning, below. "It is essential to continue research into the relationship between TERLIVAZ treatment and key factors impacting clinical outcomes, such as concomitant treatments, comorbidities, and real-world care environments, to provide further insights into the continued use of TERLIVAZ for patients with this critical condition," said Khurram Jamil, MD, Vice President, Hepatology, Clinical Development & Critical Care. "We are thrilled to be able to share findings from our 11 scientific presentations at this year's AASLD Liver Meeting with the medical community – a testament to the breadth and depth of Mallinckrodt's commitment to expanding our collective knowledge of HRS to help physicians diagnose and treat HRS patients as early and effectively as possible." Highlights of Mallinckrodt's 11 scientific presentations at the AASLD 2023 Liver Meeting include: Three Oral Presentations: Findings from a pooled analysis of the three largest-ever prospective studies to assess the safety and efficacy of TERLIVAZ in patients with HRS type 1 (HRS-1) in the U.S. and Canada (CONFIRM, REVERSE, and OT-0401) evaluating the impact of mean arterial pressure on HRS reversal from baseline to end of treatment with TERLIVAZ (Abstract #224).2 Health economics outcomes from a decision-analytic model projecting the benefit of TERLIVAZ treatment among patients with alcohol-related cirrhosis and HRS (Abstract #80).5 An analysis of the clinical outcomes associated with concomitant albumin dosing with TERLIVAZ for the treatment of HRS-acute kidney injury (HRS-AKI) (Abstract #211).3 One AASLD Poster of Distinction: Results from a post hoc analysis of the CONFIRM, REVERSE, and OT-0401 trials assessing the relationship between mean arterial pressure and TERLIVAZ in HRS-AKI reversal (Abstract #3052-A).4 Please see a complete list of Mallinckrodt-sponsored abstracts to be presented at the 2023 AASLD Liver Meeting here. Abstracts can also be found on the 2023 AASLD Liver Meeting website. Mallinckrodt will also be present at the meeting with an interactive Medical Affairs booth in the exhibit hall (Location D2825) throughout the duration of the meeting. Data collected in retrospective, pooled, database, or post hoc analyses may have errors or omissions. Outcomes may be influenced by therapies not evaluated in the study and the clinical/health economic outcomes may not be solely attributable to TERLIVAZ. 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.6 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.6 HRS involving rapid reduction in kidney function1 is estimated to affect more than 35,000 Americans annually and rates of HRS hospitalizations are increasing.7,8 If left untreated, HRS with rapid reduction in kidney function1 has a median survival time of approximately two weeks and greater than 80 percent mortality within three months.9,10 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 . Mallinckrodt uses its website as a channel of distribution of important company information, such as press releases, investor presentations and other financial information. It also uses its website to expedite public access to time-critical information regarding the company in advance of or in lieu of distributing a press release or a filing with the U.S. Securities and Exchange Commission (SEC) disclosing the same information. Therefore, investors should look to the Investor Relations page of the website for important and time-critical information. Visitors to the website can also register to receive automatic e-mail and other notifications alerting them when new information is made available on the Investor Relations page of the website. 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 impact of Mallinckrodt's pending Chapter 11 cases; 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-2300796 11/23 References 1 TERLIVAZ® (terlipressin) for Injection. Prescribing Information. Mallinckrodt Hospital Products Inc. 2023. 2 Fricker ZP, et al. Improved Mean Arterial Pressure from Baseline to the End of Treatment with Terlipressin is Associated with Hepatorenal Syndrome Reversal: A Pooled Analysis of 3 Phase III Studies. Abstract to be presented in oral presentation at the American Association for the Study of Liver Diseases (AASLD) 2023 The Liver Meeting. November 2023. 3 Wong F, et al. Albumin Dosing with Terlipressin for the Treatment of HRS-AKI: A Double-Edged Sword. Abstract to be presented in oral presentation at the American Association for the Study of Liver Diseases (AASLD) 2023 The Liver Meeting. November 2023. 4 Cullaro G, et al. Understanding the Relationship Between Mean Arterial Pressure and Terlipressin in Hepatorenal Syndrome-Acute Kidney Injury Reversal: A Post Hoc Analysis of the CONFIRM, REVERSE, and OT-0401 Trials. Poster of Distinction to be presented in oral presentation at the American Association for the Study of Liver Diseases (AASLD) 2023 The Liver Meeting. November 2023. 5 Mumtaz K, et al. Decision-Analytic Model to Project the Benefit of Terlipressin Treatment Among Patients with Alcohol-Related Cirrhosis and HRS. Abstract to be presented in oral presentation at the American Association for the Study of Liver Diseases (AASLD) 2023 The Liver Meeting. November 2023. 6 National Organization for Rare Disorders. Hepatorenal Syndrome. Available at: . Accessed October 2023. 7 Data on file – Ref-06931. Mallinckrodt Pharmaceuticals. 8 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;53:1. doi.org/10/1080/07853890 9 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. . 10 Boyer TD, et al. Terlipressin Plus Albumin Is More Effective Than Albumin Alone in Improving Renal Function in Patients With Cirrhosis and Hepatorenal Syndrome Type 1. Gastroenterology. 2016;150:1579-1589. SOURCE Mallinckrodt plc