Ventricular Premature Complexes

PKP2 Mutations Are the Leading Cause of ARVC, a Dangerous Condition Linked to Sudden Cardiac Arrest in Young People Estimated to Affect 70,000 People in the US TN-401 Preclinical Studies Demonstrated Robust Reduction of Ventricular Arrhythmias and Extended Survival in Knockout Models of Disease After a Single Dose SOUTH SAN FRANCISCO, Calif., Oct. 26, 2023 (GLOBE NEWSWIRE) -- Tenaya Therapeutics, Inc. (NASDAQ: TNYA), a clinical-stage biotechnology company with a mission to discover, develop and deliver potentially curative therapies that address the underlying causes of heart disease, announced today that the U.S. Food and Drug Administration (FDA) has provided clearance of the company’s Investigational New Drug (IND) application to initiate clinical testing of TN-401. TN-401 is Tenaya’s adeno-associated virus serotype 9 (AAV9)-based investigational gene therapy product candidate for the treatment of arrhythmogenic right ventricular cardiomyopathy (ARVC) caused by mutations in the plakophilin-2 (PKP2) gene. Based on this IND clearance, the company plans to initiate the RIDGE-1™ Phase 1b clinical trial of TN-401, a multi-center, open-label study to assess the safety, tolerability and clinical efficacy of a one-time intravenous infusion of TN-401. Tenaya is currently conducting the RIDGE™ global non-interventional natural history and serotype study of PKP2-associated ARVC. ARVC, also known as arrhythmogenic cardiomyopathy (ACM), is a chronic, progressive, familial disease that typically presents before age 40. People with ARVC experience symptoms related to ventricular arrhythmias, including palpitations, lightheadedness and fainting, and are at increased risk of sudden cardiac death. PKP2 mutations are the most common genetic cause of ARVC and result in a loss of key proteins needed to maintain the structural integrity and cell-to-cell signaling of heart muscle cells. TN-401 is designed to address the underlying cause of disease by delivering a fully functional PKP2 gene to restore normal PKP2 protein levels and thereby slow disease progression and reverse the course of disease after a single dose. “People with arrhythmogenic cardiomyopathy report high levels of fear and stress and must withstand burdensome physical and lifestyle restrictions in an effort to manage the frequent abnormal heart rhythms and constant risk of sudden cardiac arrest associated with their disease,” said Whit Tingley, M.D., Ph.D., Tenaya’s Chief Medical Officer. “TN-401 is intended to address the genetic mutation most frequently underlying ARVC. The initial dose for TN-401 in the RIDGE-1 study was associated with near maximal efficacy in our preclinical studies. With clinical site and patient community engagement well underway, we look forward to rapidly advancing TN-401 into the clinic.” In preclinical studies in a knock-out mouse model of disease, Tenaya’s PKP2 gene therapy administered at a dose of 3E13 vg/kg restored normal levels of PKP2 protein expression and demonstrated durable efficacy in preventing disease development and slowing or reversing disease progression after onset leading to long-term survival. AAV9 was selected as the vector for delivery of Tenaya’s PKP2 gene therapy based on its extensive clinical and commercial safety record in thousands of patients globally and its demonstrated ability in clinical studies to broadly distribute around the human heart and robustly express in heart muscle cells. Tenaya has completed cGMP drug product manufacturing at the 1000-liter scale for TN-401 at the company’s Genetic Medicines Manufacturing Center, with sufficient drug product produced to support the entire Phase 1b study. TN-401 RIDGE-1 Phase 1b Protocol Tenaya’s RIDGE-1 Phase 1b clinical trial of TN-401 is a multi-center, open-label study to assess the safety, tolerability and clinical efficacy of a one-time intravenous infusion of TN-401. The RIDGE-1 clinical trial will seek to enroll up to fifteen adults who have been diagnosed with PKP2-associated ARVC. Trial participants must have an implantable cardioverter defibrillator (ICD) and be at increased risk for arrhythmias as determined during screening by premature ventricular contraction (PVC) count. The trial will be conducted in two stages, with dose administration and outpatient assessments through 52-weeks and a long-term follow-up segment for four-years thereafter. Enrollment will be divided into two dose cohorts, starting at a dose of 3E13 vg/kg, a dose associated with near-maximal efficacy in preclinical studies. Following dosing of the first three patients, a panel of independent safety reviewers will advise on plans to dose escalate and expand enrollment of the initial cohort. The trial protocol includes assessments of safety, markers of cardiac transduction and transgene expression in right ventricular biopsy samples, changes in PVC, sustained or non-sustained ventricular tachycardia (VT or NSVT) occurrences, circulating plasma biomarkers, imaging biomarkers of disease as measured by echocardiogram and patient-reported outcomes. About PKP2-Associated ARVC Plakophilin-2 (PKP2) mutations are the most common genetic cause of arrhythmogenic right ventricular cardiomyopathy (ARVC), estimated to represent approximately 40 percent of the overall ARVC population. The prevalence of PKP2-associated ARVC is estimated at more than 70,000 people in the U.S. alone, though it frequently goes undiagnosed as sudden cardiac death is the first sign of disease in nearly one quarter of known cases. In PKP2-associated ARVC, mutations of the PKP2 gene results in insufficient expression of a protein needed for the proper functioning of the desmosomal complex that maintains physical connections and electrical signaling between heart muscle cells. As the desmosome structure degrades, cardiac muscle cells are replaced by fibrofatty tissue and electrical pulses in the heart become unstable, resulting in adverse remodeling and irregular heart rhythms. ARVC symptoms include arrhythmias, palpitations, lightheadedness, dizziness and fainting. It is typically diagnosed before age 40, and sudden cardiac arrest due to life-threatening ventricular arrhythmias is frequently the first manifestation of disease. Current treatments include anti-arrhythmic medications, implantable cardioverter-defibrillators (ICDs) and ablation procedures, which do not address the underlying genetic cause of disease. About TN-401 Gene Therapy and the RIDGE Clinical Program TN-401 is an investigational adeno-associated virus serotype 9 (AAV9)-based gene therapy being developed for the treatment of ARVC due to disease causing variants in the PKP2 gene. AAV9 was selected as the vector for delivery of Tenaya’s PKP2 gene therapy based on its extensive clinical and commercial safety record and demonstrated ability to target heart muscle cells. In preclinical studies, Tenaya has shown that a single dose of TN-401 restored normal levels of PKP2, normalized heart rhythms, improved right and left ventricular size and function and extended survival. Tenaya has received clearance from the FDA to initiate its first-in-human RIDGE-1TM Phase 1b clinical trial of TN-401 in patients with PKP2-associated ARVC. To support TN-401’s clinical development, the company is currently enrolling the RIDGETM global non-interventional study to collect natural history and AAV9 antibody (seroprevalence) data among PKP2 gene mutation carriers with ARVC. TN-401 has received Orphan Drug Designation from the FDA. About Tenaya Therapeutics Tenaya Therapeutics is a clinical-stage biotechnology company committed to a bold mission: to discover, develop and deliver potentially curative therapies that address the underlying drivers of heart disease. Leveraging its integrated and interrelated Gene Therapy, Cellular Regeneration and Precision Medicine platforms and proprietary core capabilities, the company is advancing a pipeline of novel therapies with diverse treatment modalities for rare genetic cardiovascular disorders and more prevalent heart conditions. Tenaya’s most advanced candidates include TN-201, a gene therapy for MYBPC3-associated hypertrophic cardiomyopathy (HCM), TN-401, a gene therapy for PKP2-associated arrhythmogenic right ventricular cardiomyopathy (ARVC), and TN-301, a small molecule HDAC6 inhibitor being initially developed for heart failure with preserved ejection fraction (HFpEF). Tenaya also has multiple early-stage programs progressing through preclinical development. For more information, visit . Forward-looking Statement This press release contains forward-looking statements as that term is defined in Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Statements in this press release that are not purely historical are forward-looking statements. Words such as “plans,” “look forward,” “will,” and similar expressions are intended to identify forward-looking statements. Such forward-looking statements include, among other things, the plan to rapidly initiate RIDGE-1, a Phase 1b clinical trial of TN-401; the clinical and therapeutic potential of TN-401 as a treatment to address the genetic mutation most frequently underlying ARVC; enrollment targets for RIDGE-1; and clinical development plans for TN-401 and statements by Tenaya’s Chief Medical Officer. The forward-looking statements contained herein are based upon Tenaya’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. These forward-looking statements are neither promises nor guarantees and are subject to a variety of risks and uncertainties, including but not limited to: the impact of any future communications from the FDA regarding Tenaya’s TN-401 IND; the costs of conducting clinical trials; Tenaya’s ability to execute on its clinical development plans for TN-401; the potential failure of TN-401 to demonstrate safety and/or efficacy in clinical testing; the potential for RIDGE-1 initial clinical trial results to differ from preclinical or expected results; the timing, scope and likelihood of regulatory filings and approvals for TN-401; Tenaya’s ability to successfully operate a manufacturing facility for clinical supply for TN-401; risks associated with the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics and operating as an early stage company; Tenaya’s ability to develop, initiate or complete preclinical studies and clinical trials, and obtain approvals, for any of its product candidates; Tenaya’s continuing compliance with applicable legal and regulatory requirements; Tenaya’s ability to raise any additional funding it will need to continue to pursue its business and product development plans; Tenaya’s reliance on third parties; Tenaya’s commercialization and marketing capabilities and strategy; the loss of key scientific or management personnel; competition in the industry in which Tenaya operates; Tenaya’s ability to obtain and maintain intellectual property protection for its product candidates; general economic and market conditions; and other risks. Information regarding the foregoing and additional risks may be found in the section entitled “Risk Factors” in documents that Tenaya files from time to time with the Securities and Exchange Commission. These forward-looking statements are made as of the date of this press release, and Tenaya assumes no obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law. Contacts Michelle Corral VP, Corporate Communications and Investor Relations IR@tenayathera.com Investors Julie Seidel Stern Investor Relations Julie.seidel@SternIR.com Media Wendy Ryan Ten Bridge Communications wendy@tenbridgecommunications.com

DUBLIN, Oct. 20, 2023 /PRNewswire/ -- The "Cardiac AI Monitoring and Diagnostics Market - A Global and Regional Analysis: Focus on Product, Type, Application, End User, and Country Analysis - Analysis and Forecast, 2023-2032" report has been added to ResearchAndMarkets.com's offering. The global cardiac AI monitoring and diagnostics market was valued at $1,010.5 million in 2022 and is anticipated to reach $10,666.5 million by 2032, witnessing a CAGR of 26.88% during the forecast period 2023-2032. Cardiac AI monitoring and diagnostics involve the application of artificial intelligence (AI) technologies in the field of cardiology to monitor, analyze, and diagnose various cardiac conditions. AI algorithms are trained using extensive datasets of cardiac images, patient data, and clinical outcomes to create models that can assist healthcare professionals in interpreting cardiac diagnostic tests and making treatment decisions. This emerging medical technology aims to enhance the accuracy, efficiency, and accessibility of cardiac care. Several key factors are driving the growth of the global cardiac AI monitoring and diagnostics market. These include the significant burden of cardiovascular diseases worldwide, increasing government initiatives to promote AI adoption, growing research in AI for cardiology, rising regulatory approvals for AI-based cardiac diagnostic medical devices, and ongoing technological advancements in the field of cardiac AI diagnostics. The North American region holds the largest share in the global cardiac AI monitoring and diagnostics market. This can be attributed to factors such as an already established and technologically advanced healthcare system and high levels of digital adoption. Additionally, the Asia-Pacific region is expected to experience substantial growth during the forecast period from 2023 to 2032. This growth is driven by factors like a shortage of healthcare professionals leading to increased demand for AI-driven automation and the rising prevalence of cardiovascular diseases, which is driving demand for advanced technologies. During the COVID-19 pandemic, AI technology played a crucial role in predicting congestive heart failure in COVID-19 patients by analyzing vital signs related to heart disease. It also assisted in assessing patients' medical history and recommending appropriate medications for treatment. Furthermore, the pandemic underscored the advantages of implementing AI in cardiology. As a result, the COVID-19 crisis had a positive impact on the overall cardiac AI monitoring and diagnostics market, as it heightened the focus on remote monitoring, increased demand for early detection and proactive care, and accelerated technological advancements in cardiac diagnosis and monitoring. Market Segmentation Software to Dominate the Global Cardiac AI Monitoring and Diagnostics Market Software: Software plays a critical role in the development of AI-based medical devices. AI-based medical devices rely on sophisticated software tools that are designed to analyze medical data, images, and other inputs to provide accurate monitoring, diagnosis, and provide treatment recommendations. These software tools typically include machine learning and deep learning algorithms that are trained on large datasets of medical images and clinical data to identify patterns and predictions. Hardware: Hardware for cardiac monitoring and diagnosis includes the combination of artificial intelligence (AI) algorithms and specialized hardware devices designed to enhance the accuracy, efficiency, and accessibility of cardiac healthcare. These hardware devices are specifically developed to integrate AI capabilities into the monitoring and diagnostic processes, enabling advanced data analysis, real-time insights, and improved patient care. Cardiac Diagnostics Occupy the Largest Share in the Global Cardiac AI Monitoring and Diagnostics Cardiac Diagnostics: Cardiac diagnostics refers to the process of identifying and determining the presence, nature, and extent of cardiac diseases or abnormalities in an individual. The goal of cardiac diagnosis is to accurately identify the underlying cardiac condition, which helps guide appropriate treatment and management strategies. The integration of artificial intelligence (AI) into cardiac diagnosis involves leveraging AI algorithms and techniques to augment and enhance the diagnostic process. It has the potential to enhance accuracy, efficiency, and accessibility while supporting healthcare professionals in providing optimal care to patients. AI can help in cardiac diagnosis by performing data analysis of large volumes of cardiac data, including medical records, images, test results, and patient characteristics, analyzing medical images, such as echocardiograms, angiograms, or cardiac MRI scans, analyzing electrocardiogram (ECG) signals to detect and classify various arrhythmias and other cardiac abnormalities, or by providing AI-based decision support. Cardiac Monitoring: Cardiac monitoring refers to the continuous or periodic monitoring of a patient's heart activity, typically through the use of specialized devices or systems. It involves the recording, analysis, and interpretation of various cardiac parameters to assess heart function, detect abnormalities, and monitor cardiac conditions. The integration of AI into monitoring devices or systems enhances the accuracy, efficiency, and insights derived from the collected data. By leveraging AI algorithms, healthcare professionals can gain a deeper understanding, make timely interventions, and provide more targeted care to individuals with cardiac conditions, ultimately improving patient outcomes and quality of life. Ischemic Heart Diseases/CAD Segment to Hold the Highest Share of the Market due to the High Prevalence Ischemic Heart Diseases/CAD: Ischemic heart disease, also known as coronary artery disease (CAD), is a condition that occurs when the blood vessels supplying blood to the heart (coronary arteries) become narrowed or blocked, leading to reduced blood flow and oxygen to the heart muscle. CAD is the most common type of heart disease and a leading cause of heart attacks. The primary cause of CAD is atherosclerosis, a condition characterized by the buildup of plaque on the inner walls of the coronary arteries. Plaque consists of cholesterol, fat, calcium, and other substances. Over time, the plaque can harden and narrow the arteries, restricting blood flow. The increased prevalence of ischemic heart disease is fueling the demand for advanced solutions for monitoring and diagnosis, which is expected to propel the growth of the segment. Cardiac Arrhythmias: Cardiac arrhythmia refers to abnormal heart rhythms or irregular heartbeats. The normal rhythm of the heart is maintained by electrical signals that coordinate the contractions of the heart's chambers. When these electrical signals are disrupted, it can lead to various types of arrhythmias. Some common types of arrhythmias include atrial fibrillation (AF), ventricular tachycardia (VT), ventricular fibrillation (VF), supraventricular tachycardia (SVT), bradycardia, and premature ventricular contractions (PVCs). Ischemic Stroke: An ischemic stroke is the most common type of stroke, accounting for about 80% of all strokes. It occurs when a blood clot or plaque buildup blocks or narrows a blood vessel, reducing or completely cutting off blood flow to a part of the brain. Without an adequate blood supply, the affected brain tissue is deprived of oxygen and nutrients, leading to damage and cell death. Others: The others segment consists of other cardiac conditions such as hypertensive heart diseases, cardiomyopathy, valvular heart diseases, congenital heart diseases, and peripheral artery diseases, among others. AI has great potential to significantly impact the diagnosis and monitoring of these cardiac diseases, and several market players are working toward the implementation of AI for the diagnosis and monitoring of different cardiac diseases. Hospitals to Dominate the Global Cardiac AI Monitoring and Diagnostics Market (by End User) Based on end users, the hospital segment is expected to dominate the cardiac AI monitoring and diagnostics market. The hospitals segment held a share of 58.22% in 2022 and is expected to grow at a CAGR of 26.06% during the forecast period 2023-2032. Hospitals are one of the primary end users of the cardiac AI monitoring and diagnostics market. By leveraging AI technology, these devices can assist healthcare professionals in detecting abnormalities, predicting cardiac events, and aiding in the diagnosis of various cardiac conditions Business Dynamics Business Drivers High Burden of Cardiovascular Diseases Worldwide Increasing Government Initiatives for AI Adoption Growing Research in the Field of AI for Cardiology Increasing Regulatory Approvals of Cardiac Diagnostics AI Medical Devices Technological Advancements in the Field of Cardiac AI Diagnostics Business Restraints Hesitation in Adoption and Acceptance of AI-Enabled Solutions for Cardiac Diagnosis Business Opportunities Increasing Opportunities for AI-Enabled Cardiac Diagnosis Solutions in Emerging Economies Partnerships and Alliances amongst Market Players Creating an Opportunity for Growth Key Trends Rising Number of Startups in the Market Increased Awareness Regarding Preventative Measures and Personalized Treatment Growing Demand for Wearable Sensors for Cardiac Monitoring Leading to Increased Adoption of AI-Enabled Solutions for Home-Based Care Key Companies Profiled: AliveCor Inc. Aidoc Boston Scientific Corporation Canon Inc. CathWorks Circle Cardiovascular Imaging Inc. General Electric Company HeartFlow, Inc. iRhythm Technologies, Inc. Koninklijke Philips N.V. Medicalgorithmics S.A. Nanox.AI Ltd. Siemens Healthineers AG Tempus Labs, Inc. Ultromics Limited. Viz.ai, Inc. Case Studies Case Study 1: Ultromics Limited The EchoGo System Developement Use Case and Reliability A Success Story Partners and Recognitions Case Study 2: CorVista Health, Inc. The CorVista System A Success Story Ongoing Clinical Trials Funding Scenario End User Perception Entry Barriers for New Entrants Patent Analysis Awaited Technological Developments Patent Analysis (by Country) Patent Analysis (by Year) Business Models Cardiac AI Monitoring and Diagnostics Market Impacts Improved Accuracy and Efficiency Early Detection of Heart Condition Remote Patient Monitoring Personalized Treatment Plans Bridging Healthcare Gaps Research and Development Cost Savings Impact of COVID-19 Impact on the Overall Market Pre-COVID-19 Scenario During COVID-19 Scenario Post COVID-19 Scenario For more information about this report visit About ResearchAndMarkets.com ResearchAndMarkets.com is the world's leading source for international market research reports and market data. We provide you with the latest data on international and regional markets, key industries, the top companies, new products and the latest trends. 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Strategic effort aims to bring stable, quality supply to providers and enhanced pricing predictability for critical labor and delivery drug CHARLOTTE, N.C. and DUBLIN, July 17, 2023 /PRNewswire/ -- Endo International plc (OTC: ENDPQ) and Premier, Inc. (NASDAQ: PINC) announced today that Endo's Par Sterile Products business will supply Pitocin® (oxytocin injection, USP) vials through Premier's ProvideGx® and PremierProRx® programs. Pitocin® is used to induce labor in pregnant women. The product is on the World Health Organization's essential medications list and has a history of supply disruptions, which can result in potential health risks to mothers and babies, as well as costly delays in hospital labor and delivery wards. The partnership involves a multifaceted approach seeking to provide stable product supply through adequate safety stock on a long-term basis. "We're pleased to offer Pitocin® injection through the robust and highly reliable ProvideGx® and PremierProRx® supply channels," said Scott Sims, Senior Vice President and General Manager, Injectable Solutions & Generics at Endo. "As a long-standing collaborator with Premier, we're proud to join the organization in helping to address drug shortages and serving as a reliable supplier of this labor and delivery product." "This initiative with Endo is yet another step forward to help eliminate drug shortages for our healthcare provider members, create increased market competition and promote more predictable, long-term prices," said Michael J. Alkire, President and CEO of Premier. "Both ProvideGx® and the PremierProRx® private label program are building a more diversified pharmaceutical market designed to create sustainable supply of a drug vital for maternal care and health in the U.S." Guided by health systems with more than 1,600 hospitals across the nation, Premier's ProvideGx® and PremierProRx® programs create long-term committed buying contracts with participating manufacturers—creating a steady demand signal and guaranteed buyer base in exchange for increasing production of generics in shortage, maintaining safety stocks or diversifying supply sources. These programs offer members access to more than 150 drugs that are or have been recently designated as shortage drugs, and have successfully helped resolve 14 drug shortages, resulting in their official delisting from the U.S. Food & Drug Administration's shortage list. With a stable supply of Pitocin®, Premier can continue efforts aimed at addressing factors that impact maternal and infant health outcomes, including the PINC AI™ Perinatal Improvement Collaborative that brings together more than 220 health systems in all 50 states using performance improvement tools and standardized data to measure outcomes and help identify the drivers of maternal mortality and morbidity. IMPORTANT SAFETY INFORMATION CONTRAINDICATIONS Antepartum use of Pitocin is contraindicated in any of the following circumstances: Where there is significant cephalopelvic disproportion; In unfavorable fetal positions or presentations, such as transverse lies, which are undeliverable without conversion prior to delivery; In obstetrical emergencies where the benefit-to-risk ratio for either the fetus or the mother favors surgical intervention; In fetal distress where delivery is not imminent; Where adequate uterine activity fails to achieve satisfactory progress; Where the uterus is already hyperactive or hypertonic; In cases where vaginal delivery is contraindicated, such as invasive cervical carcinoma, active herpes genitalis, total placenta previa, vasa previa, and cord presentation or prolapse of the cord; In patients with hypersensitivity to the drug. WARNINGS Pitocin, when given for induction of labor or augmentation of uterine activity, should be administered only by the intravenous route and with adequate medical supervision in a hospital. PRECAUTIONS All patients receiving intravenous oxytocin must be under continuous observation by trained personnel who have a thorough knowledge of the drug and are qualified to identify complications. Electronic fetal monitoring provides the best means for early detection of overdosage. When properly administered, oxytocin should stimulate uterine contractions comparable to those seen in normal labor. Overstimulation of the uterus by improper administration can be hazardous to both mother and fetus. Even with proper administration and adequate supervision, hypertonic contractions can occur in patients whose uteri are hypersensitive to oxytocin. This fact must be considered by the physician in exercising his judgment regarding patient selection. Oxytocin should not be administered in the following conditions: fetal distress, hydramnios, partial placenta previa, prematurity, borderline cephalopelvic disproportion, and any condition in which there is a predisposition for uterine rupture, such as previous major surgery on the cervix or uterus including cesarean section, overdistention of the uterus, grand multiparity, or past history of uterine sepsis or of traumatic delivery. The decision can be made only by carefully weighing the potential benefits which oxytocin can provide in a given case against rare but definite potential for the drug to produce hypertonicity or tetanic spasm. Maternal deaths due to hypertensive episodes, subarachnoid hemorrhage, rupture of the uterus, and fetal deaths due to various causes have been reported associated with the use of parenteral oxytocic drugs for induction of labor or for augmentation in the first and second stages of labor. Oxytocin has been shown to have an intrinsic antidiuretic effect, acting to increase water reabsorption from the glomerular filtrate. Consideration should, therefore, be given to the possibility of water intoxication, particularly when oxytocin is administered continuously by infusion and the patient is receiving fluids by mouth. When oxytocin is used for induction or reinforcement of already existent labor, patients should be carefully selected. Pelvic adequacy must be considered and maternal and fetal conditions evaluated before use of the drug. ADVERSE REACTIONS The following adverse reactions have been reported in the mother: Anaphylactic reaction, postpartum hemorrhage, cardiac arrhythmia, fatal afibrinogenemia, nausea, vomiting, premature ventricular contractions, pelvic hematoma, subarachnoid hemorrhage, hypertensive episodes, and rupture of the uterus. The following adverse reactions have been reported in the fetus or neonate: Due to induced uterine motility: Bradycardia, premature ventricular contractions and other arrhythmias, permanent CNS or brain damage, fetal death, and neonatal seizures have been reported with the use of Pitocin. Due to use of oxytocin in the mother: Low Apgar scores at five minutes, neonatal jaundice, and neonatal retinal hemorrhage. DRUG INTERACTIONS Severe hypertension has been reported when oxytocin was given three to four hours following prophylactic administration of a vasoconstrictor in conjunction with caudal block anesthesia. Cyclopropane anesthesia may modify oxytocin's cardiovascular effects, so as to produce unexpected results such as hypotension. Maternal sinus bradycardia with abnormal atrioventricular rhythms has also been noted when oxytocin was used concomitantly with cyclopropane anesthesia. INDICATIONS AND USAGE Antepartum: Pitocin is indicated for the initiation or improvement of uterine contractions, where this is desirable and considered suitable for reasons of fetal or maternal concern, in order to achieve vaginal delivery. It is indicated for (1) induction of labor in patients with a medical indication for the initiation of labor, such as Rh problems, maternal diabetes, preeclampsia at or near term, when delivery is in the best interests of mother and fetus or when membranes are prematurely ruptured and delivery is indicated; (2) stimulation or reinforcement of labor, as in selected cases of uterine inertia; (3) as adjunctive therapy in the management of incomplete or inevitable abortion. In the first trimester, curettage is generally considered primary therapy. In second trimester abortion, oxytocin infusion will often be successful in emptying the uterus. Other means of therapy, however, may be required in such cases. Postpartum: Pitocin is indicated to produce uterine contractions during the third stage of labor and to control postpartum bleeding or hemorrhage. Please click for full Prescribing Information. About Endo Endo (OTC: ENDPQ) is a specialty pharmaceutical company committed to helping everyone we serve live their best life through the delivery of quality, life-enhancing therapies. Our decades of proven success come from passionate team members around the globe collaborating to bring treatments forward. Together, we boldly transform insights into treatments benefiting those who need them, when they need them. Learn more at or connect with us on LinkedIn. About Premier, Inc. Premier, Inc. (NASDAQ: PINC) is a leading healthcare improvement company, uniting an alliance of more than 4,400 U.S. hospitals and health systems and approximately 250,000 other providers to transform healthcare. With integrated data and analytics, collaboratives, supply chain solutions, and consulting and other services, Premier enables better care and outcomes at a lower cost. Premier plays a critical role in the rapidly evolving healthcare industry, collaborating with members to co-develop long-term innovations that reinvent and improve the way care is delivered to patients nationwide. Headquartered in Charlotte, N.C., Premier is passionate about transforming American healthcare. Please visit Premier's news and investor sites on ; as well as Twitter, Facebook, LinkedIn, YouTube, Instagram and Premier's blog for more information about the company. Cautionary Note Regarding Forward-Looking Statements Certain information in this press release may be considered "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 and any applicable Canadian securities legislation including, but not limited to, the statements by Messrs. Sims and Alkire, any statements relating to product supply, reliability, availability or pricing, and any statements that refer to expected, estimated or anticipated future results or that do not relate solely to historical facts. Statements including words or phrases such as "believe," "expect," "anticipate," "intend," "estimate," "plan," "will," "may," "look forward," "intend," "guidance," "future," "potential" or similar expressions are forward-looking statements. All forward-looking statements in this communication reflect Endo's (the "Company's") current views as of the date of this communication about its plans, intentions, expectations, strategies and prospects, which are based on the information currently available to it and on assumptions it has made. Actual results may differ materially and adversely from current expectations based on a number of factors, including, among other things, the outcome of the Company's contingency planning and restructuring activities; the timing, impact or results of any pending or future litigation, investigations, proceedings or claims, including opioid, tax and antitrust related matters; any actual or contingent liabilities; settlement discussions or negotiations; the Company's liquidity, financial performance, cash position and operations; the risks and uncertainties associated with chapter 11 proceedings; the time, terms and ability to confirm a sale of the Company's businesses under Section 363 of the U.S. Bankruptcy Code; the risk that the Company's chapter 11 cases may be converted to cases under chapter 7 of the Bankruptcy Code; the adequacy of the capital resources of the Company's businesses and the difficulty in forecasting the liquidity requirements of the operations of the Company's businesses; the unpredictability of the Company's financial results; the Company's ability to discharge claims in chapter 11 proceedings; negotiations with the holders of the Company's indebtedness and its trade creditors and other significant creditors; the risks and uncertainties with performing under the terms of the restructuring support agreement and any other arrangement with lenders or creditors while in chapter 11 proceedings; the performance, including the approval, introduction, and consumer and physician acceptance of new products and the continuing acceptance of currently marketed products; and the Company's ability to obtain and successfully manufacture, maintain and distribute a sufficient supply of products to meet market demand in a timely manner. The Company expressly disclaims any intent or obligation to update these forward-looking statements, except as required to do so by law. Additional information concerning risk factors, including those referenced above, can be found in press releases issued by the Company, as well as the Company's public periodic filings with the U.S. Securities and Exchange Commission and with securities regulators in Canada, including the discussion under the heading "Risk Factors" in the Company's most recent Annual Report on Form 10-K and any subsequent Quarterly Reports on Form 10-Q or other filings with the U.S. Securities and Exchange Commission. View original content to download multimedia: SOURCE Endo International plc Company Codes: NASDAQ-NMS:PINC, OTC-BB:ENDPQ, OTC-PINK:ENDPQ