Sick Sinus Syndrome

PRINCETON, N.J.--( BUSINESS WIRE )-- Bristol Myers Squibb (NYSE: BMY) today announced new data from the Phase 3 DAYBREAK trial demonstrating that decreased rates of brain volume loss were sustained in the open-label extension (OLE) for patients treated with Zeposia (ozanimod) for relapsing forms of multiple sclerosis. These findings showed that patients receiving continuous Zeposia treatment for up to five years experienced low and stable rates of whole brain volume (WBV) loss through Month 60 (annualized least squares mean [LSM] % change from parent trial baseline: RADIANCE, −0.27; SUNBEAM, −0.35). Additionally, findings from a separate DAYBREAK OLE safety analysis demonstrated declining or stable incidence rates of treatment-emergent adverse events (TEAEs), with relatively low rates of infections, serious infections and opportunistic infections over more than eight years of treatment with Zeposia . These data and 12 additional abstracts will be presented at the 40 th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Copenhagen, Denmark taking place September 18-20, 2024. “If not treated early upon diagnosis, multiple sclerosis can lead to significant, irreversible brain volume loss and cognitive decline,” said Jeffrey Cohen, MD, Mellen Center for Multiple Sclerosis, Cleveland Clinic, Cleveland, Ohio and a paid consultant for Bristol Myers Squibb. “These new analyses reinforce the well-established safety and efficacy profile of Zeposia as an effective oral therapy, especially for newly diagnosed patients living with relapsing forms of multiple sclerosis.” Reductions in brain volume loss with Zeposia treatment The DAYBREAK OLE trial included 2,257 patients from the SUNBEAM and RADIANCE Phase 3 trials and evaluated rates of brain volume loss (Poster #P1623). Switching from interferon beta-1a (IFN-β) to Zeposia treatment consistently reduced rates of WBV loss (annualized LSM% change from RADIANCE baseline to Month 24 and DAYBREAK baseline to Month 24: −0.48 and −0.19, respectively, with a similar pattern observed in SUNBEAM). Additionally, similar reductions were observed for change in thalamic volume loss. High annualized LSM% reductions in cortical grey matter volume (CGMV) were observed with IFN-β (annualized change at Month 12 relative to SUNBEAM baseline: −1.02; annualized change at Month 24 relative to RADIANCE baseline: −0.59), but this trend reversed 12 months after switching to Zeposia in DAYBREAK (annualized LSM% increase relative to DAYBREAK baseline: patients from SUNBEAM, 0.10; patients from RADIANCE, 0.20), with low annualized LSM% CGMV loss observed thereafter. Established Zeposia safety profile confirmed with more than eight years of DAYBREAK data The final DAYBREAK OLE safety analysis (Poster #P1609) included 762 patients who were treated with continuous Zeposia with a median exposure of 83.9 months. Incident rates per 1,000 person-years decreased over time from the Phase 3 trials to Month 60 or more of the DAYBREAK OLE trial. Decreases were observed for overall TEAEs (896.1 versus 101.7), infections (300.5 versus 142.6), opportunistic infections (12.0 versus 4.9), cardiac (22.8 versus 9.5), hepatic (77.0 versus 15.7) and pulmonary disorders (11.3 versus 4.7), respectively. “The data presented at ECTRIMS further reinforce the long-term safety and efficacy of Zeposia and add to the robust body of evidence demonstrating its potential impact on decreasing disease progression over time,” said Alyssa Johnsen, MD, PhD , senior vice president and head of clinical development, Immunology, Cardiovascular and Neuroscience, Bristol Myers Squibb. “Building on our expertise with Zeposia , we are expanding our pipeline as we continue to look for new ways to advance the field of neuroscience. New modalities and disease targets fuel our goal of delivering medicines that elevate standards of care across neurological diseases, including multiple sclerosis.” Bristol Myers Squibb thanks the patients and investigators who participated in the Zeposia clinical trials. About DAYBREAK DAYBREAK was a Phase 3, multi-center, long-term open-label extension study to evaluate the safety and efficacy of Zeposia (ozanimod) administered orally to patients with relapsing forms of multiple sclerosis (RMS). Eligible patients from the RADIANCE, SUNBEAM and RPC01-1001 trials diagnosed with RMS were enrolled to receive treatment until the end of the DAYBREAK. Patients in the trial received Zeposia 0.92 mg (equivalent to 1 mg). About SUNBEAM SUNBEAM was a pivotal, Phase 3, multicenter, randomized, double-blind, double-dummy, active-controlled trial evaluating the efficacy, safety and tolerability of two doses of oral Zeposia (0.92 mg and 0.46 mg, equivalent to 1 mg and 0.5 mg, respectively) against weekly intramuscular Avonex ® for at least a 12-month treatment period. The study included 1,346 people living with RMS across 152 sites in 20 countries. The primary endpoint of the trial was annualized relapse rates during the treatment period. The secondary MRI endpoints included the number of new or enlarging hyperintense T2-weighted brain MRI lesions over 12 months, number of gadolinium-enhanced brain MRI lesions at Month 12 and percent change from baseline in whole brain volume at Month 12. Cortical grey and thalamic volume changes were also prospectively assessed versus active comparator. About RADIANCE RADIANCE Part B was a pivotal, Phase 3, multicenter, randomized, double-blind, double-dummy, active-controlled trial evaluating the efficacy, safety and tolerability of oral Zeposia 0.92 mg (equivalent to 1 mg) against weekly intramuscular Avonex ® (interferon beta-1a) over a 24-month treatment period. The study included 1,320 people living with RMS across 150 sites in 21 countries. The primary endpoint of the trial was annualized relapse rates over 24 months. The secondary MRI endpoints included the number of new or enlarging hyperintense T2-weighted brain MRI lesions over 24 months. About Multiple Sclerosis Multiple sclerosis (MS) is a disabling, unpredictable disease in which the immune system attacks the protective myelin sheath that covers the nerves. The myelin damage disrupts communication between the brain and the rest of the body. Ultimately, the nerves themselves may deteriorate—a process that's currently irreversible. MS affects 700,000 people in Europe and approximately 2.9 million people worldwide. Relapsing forms of MS (RMS), including clinically isolated syndrome, relapsing remitting disease and active secondary progressive disease, is characterized by clearly defined attacks of worsening neurologic function. These attacks—often called relapses, flare-ups or exacerbations—are followed by partial or complete recovery periods. During these recovery periods, also called remissions, symptoms improve partially or completely with no apparent progression of disease. However, smoldering neuroinflammation can be present from the earliest stages of MS, which is underlying and continuous disease activity occurring simultaneously in different areas of the brain that contributes to disability accumulation. Since MS relapses are unpredictable, patients can feel frustrated, stressed or scared when they occur. RMS is the most common disease course at the time of diagnosis. Approximately 85% of patients are initially diagnosed with RMS, compared with 10%-15% diagnosed with progressive forms of the disease. Bristol Myers Squibb: Delivering Breakthrough Science for Meaningful Interventions in Neuroscience Neurological conditions represent some of the greatest challenges of our time because of their impact on society, including patients, caregivers, families and healthcare systems. At Bristol Myers Squibb, we are committed to advancing our robust pipeline of potential medicines for neurological disorders with the goal of modifying disease and improving quality of life. Leveraging genetics, biomarkers and predictive sciences, we target key pathways involved in the initiation and progression of neurological diseases to develop therapies with the potential to optimize patient outcomes. About Zeposia (ozanimod) Zeposia (ozanimod) is an oral, sphingosine 1-phosphate (S1P) receptor modulator that binds with high affinity to S1P receptors 1 and 5. Zeposia blocks the capacity of lymphocytes to egress from lymph nodes, reducing the number of lymphocytes in peripheral blood. The mechanism by which Zeposia exerts therapeutic effects in multiple sclerosis (MS) is unknown but may involve the reduction of lymphocyte migration into the central nervous system. Zeposia is approved in numerous countries around the world for the treatment of adults with relapsing forms of MS and adults with moderately to severely active ulcerative colitis. U.S. FDA APPROVED INDICATIONS ZEPOSIA ® (ozanimod) is indicated for the treatment of: Relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. Moderately to severely active ulcerative colitis (UC) in adults. IMPORTANT SAFETY INFORMATION Contraindications: Patients who in the last 6 months, experienced myocardial infarction, unstable angina, stroke, transient ischemic attack (TIA), decompensated heart failure requiring hospitalization, or Class III/IV heart failure or have a presence of Mobitz type II second-degree or third-degree atrioventricular (AV) block, sick sinus syndrome, or sino-atrial block, unless the patient has a functioning pacemaker Patients with severe untreated sleep apnea Patients taking a monoamine oxidase (MAO) inhibitor Infections: ZEPOSIA may increase the susceptibility to infections. Life-threatening and rare fatal infections have occurred in patients receiving ZEPOSIA. Obtain a recent (i.e., within 6 months or after discontinuation of prior MS or UC therapy) complete blood count (CBC) including lymphocyte count before initiation of ZEPOSIA. Delay initiation of ZEPOSIA in patients with an active infection until the infection is resolved. Consider interruption of treatment with ZEPOSIA if a patient develops a serious infection. Continue monitoring for infections up to 3 months after discontinuing ZEPOSIA. Herpes zoster was reported as an adverse reaction in ZEPOSIA-treated patients. Herpes simplex encephalitis and varicella zoster meningitis have been reported with sphingosine 1-phosphate (S1P) receptor modulators. Patients without a healthcare professional-confirmed history of varicella (chickenpox), or without documentation of a full course of vaccination against varicella zoster virus (VZV), should be tested for antibodies to VZV before initiating ZEPOSIA. A full course of vaccination for antibody-negative patients with varicella vaccine is recommended prior to commencing treatment with ZEPOSIA. Cases of fatal cryptococcal meningitis (CM) were reported in patients treated with another S1P receptor modulator. If CM is suspected, ZEPOSIA should be suspended until cryptococcal infection has been excluded. If CM is diagnosed, appropriate treatment should be initiated. In the MS and UC clinical studies, patients who received ZEPOSIA were not to receive concomitant treatment with antineoplastic, non-corticosteroid immunosuppressive, or immune-modulating therapies used for treatment of MS and UC. Concomitant use of ZEPOSIA with any of these therapies would be expected to increase the risk of immunosuppression. When switching to ZEPOSIA from immunosuppressive medications, consider the duration of their effects and their mode of action to avoid unintended additive immunosuppressive effects. Use of live attenuated vaccines should be avoided during and for 3 months after treatment with ZEPOSIA. If live attenuated vaccine immunizations are required, administer at least 1 month prior to initiation of ZEPOSIA. Progressive Multifocal Leukoencephalopathy (PML): PML is an opportunistic viral infection of the brain that typically occurs in patients who are immunocompromised, and that usually leads to death or severe disability. PML has been reported in patients treated with S1P receptor modulators, including ZEPOSIA, and other MS and UC therapies and has been associated with some risk factors. If PML is suspected, withhold ZEPOSIA and perform an appropriate diagnostic evaluation. If confirmed, treatment with ZEPOSIA should be discontinued. Immune reconstitution inflammatory syndrome (IRIS) has been reported in MS patients treated with S1P receptor modulators who developed PML and subsequently discontinued treatment. IRIS presents as a clinical decline in the patient’s condition that may be rapid, can lead to serious neurological complications or death, and is often associated with characteristic changes on MRI. The time to onset of IRIS in patients with PML was generally within a few months after S1P receptor modulator discontinuation. Monitoring for development of IRIS and appropriate treatment of the associated inflammation should be undertaken. Bradyarrhythmia and Atrioventricular Conduction Delays: Since initiation of ZEPOSIA may result in a transient decrease in heart rate and atrioventricular conduction delays, dose titration is recommended to help reduce cardiac effects. Initiation of ZEPOSIA without dose escalation may result in greater decreases in heart rate. If treatment with ZEPOSIA is considered, advice from a cardiologist should be sought for those individuals: with significant QT prolongation with arrhythmias requiring treatment with Class 1a or III anti-arrhythmic drugs with ischemic heart disease, heart failure, history of cardiac arrest or myocardial infarction, cerebrovascular disease, and uncontrolled hypertension with a history of Mobitz type II second-degree or higher AV block, sick sinus syndrome, or sino-atrial heart block Liver Injury: Elevations of aminotransferases may occur in patients receiving ZEPOSIA. Obtain liver function tests, if not recently available (i.e., within 6 months), before initiation of ZEPOSIA. Patients who develop symptoms suggestive of hepatic dysfunction should have hepatic enzymes checked and ZEPOSIA should be discontinued if significant liver injury is confirmed. Fetal Risk: There are no adequate and well-controlled studies in pregnant women. Based on animal studies, ZEPOSIA may cause fetal harm. Women of childbearing potential should use effective contraception to avoid pregnancy during treatment and for 3 months after stopping ZEPOSIA. Women who become pregnant while taking ZEPOSIA for MS may enroll in the ZEPOSIA pregnancy registry by calling 1-877-301-9314 or visiting www.zeposiapregnancyregistry.com . Increased Blood Pressure: Increase in systolic pressure was observed after about 3 months of treatment and persisted throughout treatment. Blood pressure should be monitored during treatment and managed appropriately. Certain foods that may contain very high amounts of tyramine could cause severe hypertension in patients taking ZEPOSIA. Patients should be advised to avoid foods containing a very large amount of tyramine while taking ZEPOSIA. Respiratory Effects: ZEPOSIA may cause a decline in pulmonary function. Spirometric evaluation of respiratory function should be performed during therapy, if clinically indicated. Macular Edema: S1P modulators have been associated with an increased risk of macular edema. Patients with a history of uveitis or diabetes mellitus are at increased risk. Patients with a history of these conditions should have an ophthalmic evaluation of the fundus, including the macula, prior to treatment initiation and regular follow-up examinations. An ophthalmic evaluation is recommended in all patients at any time if there is a change in vision. Continued use of ZEPOSIA in patients with macular edema has not been evaluated; potential benefits and risks for the individual patient should be considered if deciding whether ZEPOSIA should be discontinued. Posterior Reversible Encephalopathy Syndrome (PRES): Rare cases of PRES have been reported in patients receiving a S1P receptor modulator. If a ZEPOSIA-treated patient develops unexpected neurological or psychiatric symptoms or any symptom/sign suggestive of an increase in intracranial pressure, a complete physical and neurological examination should be conducted. Symptoms of PRES are usually reversible but may evolve into ischemic stroke or cerebral hemorrhage. Delay in diagnosis and treatment may lead to permanent neurological sequelae. If PRES is suspected, treatment with ZEPOSIA should be discontinued. Unintended Additive Immunosuppressive Effects From Prior Immunosuppressive or Immune-Modulating Drugs: When switching from drugs with prolonged immune effects, the half-life and mode of action of these drugs must be considered to avoid unintended additive immunosuppressive effects while at the same time minimizing risk of disease reactivation. Initiating treatment with ZEPOSIA after treatment with alemtuzumab is not recommended. Severe Increase in Multiple Sclerosis (MS) Disability After Stopping ZEPOSIA: In MS, severe exacerbation of disease, including disease rebound, has been rarely reported after discontinuation of a S1P receptor modulator. The possibility of severe exacerbation of disease should be considered after stopping ZEPOSIA treatment so patients should be monitored upon discontinuation. After stopping ZEPOSIA in the setting of PML, monitor for development of immune reconstitution inflammatory syndrome (PML-IRIS). Immune System Effects After Stopping ZEPOSIA: After discontinuing ZEPOSIA, the median time for lymphocyte counts to return to the normal range was 30 days with approximately 90% of patients in the normal range within 3 months. Use of immunosuppressants within this period may lead to an additive effect on the immune system, therefore caution should be applied when initiating other drugs 4 weeks after the last dose of ZEPOSIA. Most Common Adverse Reactions that occurred in the MS clinical trials of ZEPOSIA-treated patients (≥4%): upper respiratory infection, hepatic transaminase elevation, orthostatic hypotension, urinary tract infection, back pain, and hypertension. In the UC clinical trials, the most common adverse reactions that occurred in ≥4% of ZEPOSIA-treated patients and greater than in patients who received placebo were upper respiratory infection, liver test increased, and headache. Use in Specific Populations: Hepatic Impairment: Dosage adjustment in patients with mild or moderate hepatic impairment (Child-Pugh class A or B) is required, and use of ZEPOSIA in patients with severe hepatic impairment (Child-Pugh class C) is not recommended. For additional safety information, please see the full Prescribing Information and Medication Guide . About Bristol Myers Squibb Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn , Twitter , YouTube , Facebook and Instagram . Cautionary Statement Regarding Forward-Looking Statements This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 regarding, among other things, the research, development and commercialization of pharmaceutical products. All statements that are not statements of historical facts are, or may be deemed to be, forward-looking statements. Such forward-looking statements are based on current expectations and projections about our future financial results, goals, plans and objectives and involve inherent risks, assumptions and uncertainties, including internal or external factors that could delay, divert or change any of them in the next several years, that are difficult to predict, may be beyond our control and could cause our future financial results, goals, plans and objectives to differ materially from those expressed in, or implied by, the statements. These risks, assumptions, uncertainties and other factors include, among others, that results of future post-marketing studies will be consistent with the results of this study, that Zeposia (ozanimod) for the indication described in this release may not be commercially successful, any marketing approvals, if granted, may have significant limitations on their use, and that continued approval of Zeposia for such indication may be contingent upon verification and description of clinical benefit in additional confirmatory trials. No forward-looking statement can be guaranteed. Forward-looking statements in this press release should be evaluated together with the many risks and uncertainties that affect Bristol Myers Squibb’s business and market, particularly those identified in the cautionary statement and risk factors discussion in Bristol Myers Squibb’s Annual Report on Form 10-K for the year ended December 31, 2023, as updated by our subsequent Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the Securities and Exchange Commission. The forward-looking statements included in this document are made only as of the date of this document and except as otherwise required by applicable law, Bristol Myers Squibb undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events, changed circumstances or otherwise. corporatefinancial-news

– ONYDA XR is indicated for the treatment of ADHD as monotherapy or as adjunctive therapy to approved CNS stimulant medications in pediatric patients six years and older – – First non-stimulant ADHD medication, with nighttime dosing, adds to Tris Pharma’s established portfolio of leading ADHD therapies and reinforces company's commitment to individuals with ADHD – MONMOUTH JUNCTION, N.J.--(BUSINESS WIRE)-- Tris Pharma, Inc. (Tris), a commercial-stage biopharmaceutical company focused on attention deficit hyperactivity disorder (ADHD), pain, addiction and neurological disorders, today announced the U.S. Food and Drug Administration (FDA) has approved ONYDA™ XR (clonidine hydrochloride), a once-a-day extended-release oral suspension with nighttime dosing, for the treatment of ADHD as a monotherapy or as an adjunctive therapy to approved central nervous system (CNS) stimulant medications in pediatric patients six years and older. ONYDA XR is the first non-stimulant ADHD medication in Tris’ portfolio, the first-and-only liquid non-stimulant ADHD medication approved in the United States and the only approved non-stimulant ADHD medication with nighttime dosing. Non-stimulant ADHD therapies are an important option for patients who do not respond adequately to stimulant medication or experience negative side effects from them, and they are increasingly used as an effective alternative to stimulant treatments. ONYDA XR is expected to be available in pharmacies in the second half of 2024. “People with ADHD require a range of therapeutic options that are designed for their individual needs, because not every medication or type of therapy works for every patient,” said Ann Childress, M.D. “The approval of ONYDA XR, the only liquid non-stimulant ADHD medication, with nighttime dosing that shifts the release profile, is a convenient option for patients needing better ADHD control.” Tris Pharma harnessed the flexibility of its proprietary LiquiXR® technology to develop ONYDA XR, a liquid non-stimulant medication with a smooth, extended-release pro physicians can use to treat ADHD patients either alone or in combination with stimulant therapy. This product adds to Tris’ comprehensive and expanding portfolio of leading ADHD therapies that enhance patient care for individuals with the disorder. The company’s ADHD therapies are available in both oral suspension (liquid) and solid (tablet) forms for administration to children and adults. Tris continues to grow its ADHD offerings with a pipeline of new medications that could have a substantial impact for those with the disorder. “Securing FDA approval for ONYDA XR is not just an important milestone, but a testament to our unwavering commitment to innovating and improving outcomes for this patient population,” said Ketan Mehta, Founder and CEO at Tris Pharma. “Our relentless pursuit to offer a range of ADHD medicines to patients of all ages does not stop here, and we look forward to continuing to expand our portfolio in other ADHD indications.” The U.S. FDA approval of ONYDA XR is based on adequate and well-controlled studies of clonidine hydrochloride extended-release tablets. About Tris Pharma Tris Pharma is a privately held, innovation-driven biopharmaceutical company that is applying its drug development capabilities and proprietary technologies to transform the treatment of ADHD, pain, addiction and disorders of the central nervous system. Tris is an established commercial organization with a robust portfolio of best-in-class ADHD products and a promising pipeline of differentiated, near-term drug candidates. More information is available at and on LinkedIn @TrisPharma. ONYDA (Clonidine hydrochloride) PROFESSIONAL INDICATION & IMPORTANT SAFETY INFORMATION INDICATION ONYDA XR is a centrally acting alpha2-adrenergic agonist indicated for the treatment of attention deficit hyperactivity disorder (ADHD) as monotherapy or as adjunctive therapy to central nervous system (CNS) stimulant medications in pediatric patients 6 years of age and older. IMPORTANT SAFETY INFORMATION Contraindications: ONYDA is contraindicated in patients with history of a hypersensitivity reaction to clonidine. Warnings & Precautions Hypotension/Bradycardia: Treatment with ONYDA XR can cause dose-related decreases in blood pressure and heart rate. Titrate slowly and monitor vital signs frequently in patients at risk for hypotension, heart block, bradycardia, syncope, cardiovascular disease, vascular disease, cerebrovascular disease, or chronic renal failure. In patients who have a history of syncope or may have a condition that predisposes them to syncope, such as hypotension, orthostatic hypotension, bradycardia, or dehydration, advise patients to avoid becoming dehydrated or overheated. Somnolence/Sedation: Somnolence and sedation were commonly reported adverse reactions in clinical studies with clonidine hydrochloride extended-release tablets. Caution patients against operating heavy equipment or driving until they know how they respond to treatment with ONYDA XR. Advise patients to avoid use with alcohol. Cardiac Conduction Abnormalities: The sympatholytic action of clonidine may worsen sinus node dysfunction and atrioventricular (AV) block, especially in patients taking other sympatholytic drugs. There have been post-marketing reports of patients with conduction abnormalities and/or taking other sympatholytic drugs who developed severe bradycardia requiring intravenous (IV) atropine, IV isoproterenol, and temporary cardiac pacing while taking clonidine. Titrate ONYDA XR slowly and monitor vital signs frequently in patients with cardiac conduction abnormalities or patients concomitantly treated with other sympatholytic drugs. Adverse Reactions: Most common adverse reactions (incidence at least 5% and twice the rate of placebo) as monotherapy in ADHD: somnolence, fatigue, irritability, nightmare, insomnia, constipation, dry mouth. Most common adverse reactions (incidence at least 5% and twice the rate of placebo) as adjunct therapy to psychostimulant in ADHD: somnolence, fatigue, decreased appetite, dizziness. Drug Interactions: CNS Depressants: Clonidine may potentiate the CNS-depressive effects of alcohol, barbiturates, or other sedating drugs. Avoid concomitant use of CNS depressants with ONYDA XR. Tricyclic Antidepressants: Concomitant use of tricyclic antidepressants with clonidine can increase blood pressure and may counteract the hypotensive effects of clonidine. Monitor blood pressure and adjust dosage of ONYDA XR as needed. Drugs Known to Affect Sinus Node Function or AV Nodal Conduction: Avoid use of ONYDA XR with agents known to affect sinus node function or AV nodal conduction (e.g., digitalis, calcium channel blockers and beta-blockers) due to a potential for additive effects such as bradycardia and AV block. Antihypertensive drugs: Concomitant use of antihypertensive drugs with clonidine potentiates the hypotensive effects of clonidine. Monitor blood pressure and heart rate and adjust dosage of ONYDA XR accordingly in patients treated concomitantly with antihypertensives. Use in specific population: Use in patients with renal Impairment: The impact of renal impairment on the pharmacokinetics of clonidine in pediatric patients has not been assessed. The dosage of ONYDA XR must be adjusted according to the degree of impairment, and patients should be carefully monitored. Use during pregnancy: Prolonged experience with clonidine in pregnant women over several decades, based on published literature, including controlled trials, a retrospective cohort study and case reports, have not identified a drug associated risk of major birth defects, miscarriage, and adverse maternal or fetal outcomes. To monitor pregnancy outcomes in women exposed to ADHD medications, including ONYDA XR, during pregnancy, healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Psychiatric Medications at 1-866-961-2388 or visiting online at . Use during lactation: The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ONYDA XR and any potential adverse effects on the breastfed child from ONYDA XR or from the underlying maternal condition. Monitor breastfeeding infants exposed to ONYDA XR through breast milk for symptoms of hypotension and/or bradycardia such as sedation, lethargy, tachypnea, and poor feeding. To report SUSPECTED ADVERSE REACTIONS, contact Tris Pharma, Inc. at 1-732-940-0358 or FDA at 1-800-FDA-1088 or Please see ONYDA PI for full prescribing information

Five new launches reinforce Baxter’s focus on differentiated products and enhance the company’s Pharmaceuticals portfolio in critical therapeutic areas Products feature ready-to-use formulations to help support patient safety and offer added convenience for healthcare professionals DEERFIELD, Ill.--(BUSINESS WIRE)-- Baxter International Inc. (NYSE:BAX), a global leader in injectables, anesthesia and drug compounding, announced the continued expansion of its Pharmaceuticals portfolio with five injectable product launches in the U.S. “These launches demonstrate Baxter’s focus on differentiated products that address unmet patient needs in key therapeutic areas, including anti-infective and anti-hypotensive medications,” said Alok Sonig, executive vice president and group president, Pharmaceuticals, at Baxter. “We are proud to offer important new options for our customers and look forward to continuing to bring new innovations to the market.” Product launches within Baxter’s Pharmaceuticals portfolio in the U.S. include the following. For all products, please see full Indications, Important Risk Information and links to full Prescribing Information below. Norepinephrine Bitartrate in 5% Dextrose Injection in a new 16 mg/250 mL strength, which is indicated to raise blood pressure in adult patients with severe, acute hypotension. Baxter offers the first and only FDA-approved ready-to-use Norepinephrine in Dextrose, and now provides Norepinephrine in 4 mg/250 mL, 8 mg/250 mL and 16 mg/250 mL strengths. Vasopressin in 0.9% Sodium Chloride Injection, the first and only FDA-approved ready-to-use Vasopressin in a flexible container. Vasopressin uses Baxter’s proprietary sterile, closed system container, which is collapsible and does not require a vented intravenous set.1 Manufactured closed drug-delivery systems decrease the need for manual admixture and reduce the possibility of contamination.2 Vasopressin is indicated to increase blood pressure in adults with vasodilatory shock who remain hypotensive despite fluids and catecholamines. Baxter offers Vasopressin in 20 units/100 mL and 40 units/100 mL strengths. Vancomycin Injection, USP in 5% Dextrose in new 1.25 g/250 mL and 1.5 g/300 mL strengths. These launches are Baxter’s first frozen ready-to-use offerings in 250 mL and 300 mL volumes. Vancomycin is indicated for serious or severe infections caused by susceptible strains of methicillin-resistant (β-lactam-resistant) staphylococci. Baxter now offers Vancomycin in 500 mg/100 mL, 750 mg/150 mL, 1 g/200 mL, 1.25 g/250 mL and 1.5 g/300 mL strengths. Ropivacaine Hydrochloride Injection, USP in a ready-to-use, single-dose infusion bag. Ropivacaine is indicated in adults to produce local or regional anesthesia for surgery and for acute pain management. Baxter offers Ropivacaine in 200 mg/100 mL and 400 mg/200 mL strengths. Regadenoson Injection pre-filled syringe, a coronary vasodilator that is commonly used in pharmacologic stress testing. Baxter offers Regadenoson in a 0.4 mg/5 mL strength. Ready-to-use formats of standard concentrations of commonly prescribed drugs may offer operational efficiencies for healthcare providers. Compounding a drug for patient use is a multi-step, manual process that requires oversight by pharmacy staff. A ready-to-use product can simplify the preparation process and support patient safety by reducing the chance of contamination2 and avoiding potential errors that may occur when medications are compounded.3 These newly launched products are now available for use in the U.S. About Baxter Every day, millions of patients, caregivers and healthcare providers rely on Baxter’s leading portfolio of diagnostic, critical care, kidney care, nutrition, hospital and surgical products used across patient homes, hospitals, physician offices and other sites of care. For more than 90 years, we’ve been operating at the critical intersection where innovations that save and sustain lives meet the healthcare providers who make it happen. With products, digital health solutions and therapies available in more than 100 countries, Baxter’s employees worldwide are now building upon the company’s rich heritage of medical breakthroughs to advance the next generation of transformative healthcare innovations. To learn more, visit and follow us on X/Twitter, LinkedIn and Facebook. Norepinephrine Bitartrate in 5% Dextrose Injection Indications Norepinephrine Bitartrate in Dextrose Injection is indicated to raise blood pressure in adult patients with severe, acute hypotension. Important Risk Information Contraindications: None. Tissue Ischemia: Administration of Norepinephrine Bitartrate in Dextrose Injection to patients who are hypotensive from hypovolemia can result in severe peripheral and visceral vasoconstriction, decreased renal perfusion and reduced urine output, tissue hypoxia, lactic acidosis, and reduced systemic blood flow despite “normal” blood pressure. Address hypovolemia prior to initiating Norepinephrine Bitartrate in Dextrose Injection. Avoid use in patients with mesenteric or peripheral vascular thrombosis, as this may increase ischemia and extend the area of infarction. Gangrene of the extremities has occurred in patients with occlusive or thrombotic vascular disease or who received prolonged or high dose infusions. Monitor for changes to the skin of the extremities in susceptible patients. Extravasation of Norepinephrine Bitartrate in Dextrose Injection may cause necrosis and sloughing of surrounding tissue. To reduce the risk of extravasation, infuse into a large vein, check the infusion site frequently for free flow, and monitor for signs of extravasation. Avoid administration into the veins in the leg in elderly patients. Emergency Treatment of Extravasation: Infiltrate the ischemic area as soon as possible, using a syringe with a fine hypodermic needle with 5 to 10 mg of phentolamine mesylate in 10 to 15 mL of 0.9% Sodium Chloride Injection in adults. Hypotension after Abrupt Discontinuation: Sudden cessation of the infusion rate may result in marked hypotension. When discontinuing the infusion, gradually reduce the infusion rate while expanding blood volume with intravenous fluids. Cardiac Arrhythmias: Norepinephrine Bitartrate in Dextrose Injection elevates intracellular calcium concentrations and may cause arrhythmias, particularly in the setting of hypoxia or hypercarbia. Perform continuous cardiac monitoring of patients with arrhythmias. Elderly Patients: May be at a greater risk of developing adverse reactions. Adverse Reactions: Most common adverse reactions are hypertension and bradycardia. Drug Interactions: Co-administration of Norepinephrine Bitartrate in Dextrose Injection with monoamine oxidase (MAO) inhibitors or other drugs with MAO-inhibiting properties (e.g., linezolid) or with tricyclic antidepressants can cause severe, prolonged hypertension. Anti-diabetics: Norepinephrine Bitartrate in Dextrose Injection can decrease insulin sensitivity and raise blood glucose. Concomitant use of Norepinephrine Bitartrate in Dextrose Injection with halogenated anesthetics may lead to ventricular tachycardia or ventricular fibrillation. Monitor cardiac rhythm in patients receiving concomitant halogenated anesthetics. Please see accompanying full Prescribing Information for Norepinephrine Bitartrate in 5% Dextrose Injection. Vasopressin in 0.9% Sodium Chloride Injection Indications Vasopressin in Sodium Chloride Injection is indicated to increase blood pressure in adults with vasodilatory shock who remain hypotensive despite fluids and catecholamines. Important Risk Information Contraindications: Vasopressin in Sodium Chloride Injection is contraindicated in patients with a known allergy or hypersensitivity to 8-L-arginine vasopressin. Worsening Cardiac Function: A decrease in cardiac index may be observed with the use of vasopressin. Reversible Diabetes Insipidus: Patients may experience reversible diabetes insipidus, manifested by the development of polyuria, a dilute urine, and hypernatremia, after cessation of treatment with vasopressin. Monitor serum electrolytes, fluid status and urine output after vasopressin discontinuation. Some patients may require readministration of vasopressin or administration of desmopressin to correct fluid and electrolyte shifts. Adverse Reactions: The most common adverse reactions include decreased cardiac output, bradycardia, tachyarrhythmias, hyponatremia and ischemia (coronary, mesenteric, skin, digital). Drug Interactions: Pressor effects of catecholamines and Vasopressin in Sodium Chloride Injection are expected to be additive. Indomethacin may prolong effects of Vasopressin in Sodium Chloride Injection. Co-administration of ganglionic blockers or drugs causing SIADH (syndrome of inappropriate antidiuretic hormone secretion) may increase the pressor response. Co-administration of drugs causing diabetes insipidus may decrease the pressor response. Pregnancy: May induce tonic uterine contractions that could threaten the continuation of pregnancy. Please see accompanying full Prescribing Information for Vasopressin in 0.9% Sodium Chloride Injection. Vancomycin Injection, USP in 5% Dextrose Indications Vancomycin is indicated for the treatment of serious or severe infections caused by susceptible strains of methicillin-resistant (beta-lactam-resistant) staphylococci. It is indicated for penicillin-allergic patients, for patients who cannot receive or who have failed to respond to other drugs, and for infections caused by vancomycin-susceptible organisms that are resistant to other antimicrobial drugs. Vancomycin is effective in the treatment of: Infective Endocarditis (staphylococcal endocarditis; endocarditis caused by Streptococcus viridans or S. bovis, alone or in combination with an aminoglycoside; endocarditis caused by enterococci (e.g., E. faecalis), only in combination with an aminoglycoside; diphtheroid endocarditis; early-onset prosthetic valve endocarditis caused by S. epidermidis or diphtheroids in combination with either rifampin, an aminoglycoside, or both) Septicemia Skin and Skin Structure Infections Bone Infections Lower Respiratory Tract Infections To reduce the development of drug-resistant bacteria and maintain the effectiveness of vancomycin and other antibacterial drugs, vancomycin should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. Important Risk Information Contraindications: Vancomycin is contraindicated in patients with known hypersensitivity to this antibiotic. Solutions containing dextrose may be contraindicated in patients with known allergy to corn or corn products. Infusion Reactions: Rapid bolus administration (e.g., over several minutes) may be associated with exaggerated hypotension, including shock, and, rarely, cardiac arrest. During or soon after rapid infusion of vancomycin, patients may develop anaphylactoid reactions, including hypotension, wheezing, dyspnea, urticaria, or pruritus. Rapid infusion may also cause flushing of the upper body (“vancomycin infusion reaction”) or pain and muscle spasm of the chest and back. Vancomycin should be administered over a period of not less than 60 minutes. Stopping the infusion usually results in prompt cessation of these reactions. Nephrotoxicity: Systemic vancomycin exposure may result in acute kidney injury (AKI). The risk of AKI increases as systemic exposure/serum levels increase. Monitor renal function in all patients; especially with underlying renal impairment, with co-morbidities, and receiving concomitant therapy with a known nephrotoxic drug. Ototoxicity: It may be transient or permanent. It has been reported mostly in patients who have been given excessive doses, who have an underlying hearing loss, or who are receiving concomitant therapy with another ototoxic agent, such as an aminoglycoside. Vancomycin should be used with caution in patients with renal insufficiency. Severe Dermatologic Reactions: Toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), and linear IgA bullous dermatosis (LABD) have been reported. Cutaneous signs or symptoms reported include skin rashes, mucosal lesions, and blisters. Discontinue vancomycin Injection at the first appearance of signs and symptoms of TEN, SJS, DRESS, AGEP, or LABD. Dosage of vancomycin must be adjusted for patients with renal dysfunction. Clostridioides difficile associated diarrhea (CDAD): May range in severity from mild diarrhea to fatal colitis. CDAD must be considered in all patients who present with diarrhea following antibiotic use. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated. Hemorrhagic Occlusive Retinal Vasculitis: Including permanent loss of vision, occurred in patients receiving intracameral or intravitreal administration of vancomycin during or after cataract surgery. The safety and efficacy of vancomycin administered by the intracameral or the intravitreal route have not been established. Adverse Reactions: Not already mentioned above, patients have been reported to have neutropenia, phlebitis, drug fever, nausea, chills, and vasculitis in association with administration of vancomycin. Drug Interactions: Anesthetic Agents: Concomitant administration of vancomycin and anesthetic agents has been associated with erythema and histamine-like flushing and anaphylactoid reactions. Monitor renal function in patients receiving vancomycin and concurrent and/or sequential systemic or topical use of other potentially neurotoxic and/or nephrotoxic drugs, such as amphotericin B, aminoglycosides, bacitracin, polymyxin B, colistin, viomycin, or cisplatin. Please see accompanying full Prescribing Information for Vancomycin Injection, USP. Ropivacaine Hydrochloride Injection, USP Indications Ropivacaine Hydrochloride Injection is an amide local anesthetic indicated in adults for the production of local or regional anesthesia for surgery and for acute pain management. Surgical Anesthesia: epidural block for surgery including cesarean section; major nerve block; local infiltration. Acute Pain Management: epidural continuous infusion or intermittent bolus, e.g., postoperative or labor; local infiltration. Important Risk Information Contraindications: Ropivacaine Hydrochloride Injection is contraindicated in patients with a known hypersensitivity to ropivacaine or to any local anesthetic agent of the amide type. General Warning: Delay in proper management of dose-related toxicity, underventilation, and/or altered sensitivity may lead to the development of acidosis, cardiac arrest and, possibly, death. The safe and effective use of local anesthetics depends on proper dosage, correct technique, adequate precautions, and readiness for emergencies. It is essential that aspiration for blood, or cerebrospinal fluid (where applicable), be done prior to injecting any local anesthetic, both the original dose and all subsequent doses, to avoid intravascular or subarachnoid injection. Unintended Intravenous Injection: In performing Ropivacaine Hydrochloride Injection blocks, unintended intravenous injection is possible and may result in cardiac arrhythmia or cardiac arrest. Ropivacaine hydrochloride injection should be administered in incremental doses. It is not recommended for emergency situations, where a fast onset of surgical anesthesia is necessary. Intra-Articular Infusions and Risk of Chondrolysis: Intra-articular infusions of local anesthetics may cause chondrolysis. Ropivacaine Hydrochloride Injection is not approved for this use. Risk of Methemoglobinemia: Patients with glucose-6-phosphate dehydrogenase deficiency, congenital or idiopathic methemoglobinemia, cardiac or pulmonary compromise, infants under 6 months of age, and concurrent exposure to oxidizing agents or their metabolites are more susceptible to developing clinical manifestations of the condition. If local anesthetics must be used in these patients, close monitoring for symptoms and signs of methemoglobinemia is recommended. Signs of methemoglobinemia may occur immediately or may be delayed some hours after exposure. Immediate treatment is required to avert more serious central nervous system and cardiovascular adverse effects, including seizures, coma, arrhythmias, and death. Discontinue ropivacaine hydrochloride injection and any other oxidizing agents. Central Nervous System Toxicity: Careful and constant monitoring of cardiovascular and respiratory vital signs and the patient's state of consciousness should be performed after each local anesthetic injection. Hepatic Disease: Because amide-type local anesthetics such as ropivacaine are metabolized by the liver, these drugs, especially repeat doses, should be used cautiously in patients with hepatic disease. Patients with severe hepatic disease are at a greater risk of developing toxic plasma concentrations. Adverse Reactions: Most common adverse reactions (incidence ≥ 5%) are hypotension, nausea, vomiting, bradycardia, fever, pain, postoperative complications, anemia, paresthesia, headache, pruritus, and back pain. Drug Interactions: Agents structurally related to amide-type local anesthetics: Concurrent use may cause additive effects. Please see accompanying full Prescribing Information for Ropivacaine Hydrochloride Injection, USP. Regadenoson Injection Indications Regadenoson injection is a pharmacologic stress agent indicated for radionuclide myocardial perfusion imaging (MPI) in patients unable to undergo adequate exercise stress. Important Risk Information Contraindications: Do not administer regadenoson injection to patients with: Second- or third-degree AV block, or Sinus node dysfunction, unless these patients have a functioning artificial pacemaker. Myocardial Ischemia: Fatal cardiac events have occurred. Avoid use in patients with symptoms or signs of acute myocardial ischemia, for example unstable angina or cardiovascular instability, who may be at greater risk. Cardiac resuscitation equipment and trained staff should be available before administration. Sinoatrial (SA) and Atrioventricular (AV) Nodal Block: Adenosine receptor agonists, including regadenoson injection, can depress the SA and AV nodes and may cause first-, second- or third-degree AV block, or sinus bradycardia. Atrial Fibrillation/Atrial Flutter: New-onset or recurrent atrial fibrillation with rapid ventricular response and atrial flutter have been reported. Hypersensitivity, Including Anaphylaxis: Anaphylaxis, angioedema, cardiac or respiratory arrest, respiratory distress, decreased oxygen saturation, hypotension, throat tightness, urticaria and rashes have occurred. Have personnel and resuscitative equipment immediately available. Hypotension: Adenosine receptor agonists, including regadenoson injection, induce vasodilation and hypotension. The risk of serious hypotension may be higher in patients with autonomic dysfunction, stenotic valvular heart disease, pericarditis or pericardial effusions, stenotic carotid artery disease with cerebrovascular insufficiency, or hypovolemia. Hypertension: Adenosine receptor agonists, including regadenoson injection, may induce clinically significant increases in blood pressure particularly in patients with a history of hypertension and when the MPI includes low level exercise. Bronchoconstriction: Adenosine receptor agonists, including regadenoson injection, may induce dyspnea, bronchoconstriction and respiratory compromise, especially in patients with chronic obstructive pulmonary disease (COPD) or asthma. Resuscitative measures should be available. Seizure: Regadenoson injection may lower the seizure threshold. New onset or recurrence of convulsive seizures has occurred. Some seizures are prolonged and require urgent anticonvulsive management. Methylxanthine use is not recommended in patients who experience a seizure in association with regadenoson injection. Cerebrovascular Accident (Stroke): Hemorrhagic and ischemic cerebrovascular accidents have occurred. Adverse Reactions: The most common (incidence ≥ 5%) adverse reactions to regadenoson injection are dyspnea, headache, flushing, chest discomfort, dizziness, angina pectoris, chest pain, and nausea. Drug Interactions: Methylxanthines, e.g., caffeine, aminophylline and theophylline, interfere with the activity of regadenoson injection. Aminophylline may be used to attenuate severe and/or persistent adverse reactions to regadenoson injection. Dipyridamole may increase the activity of regadenoson injection. When possible, withhold dipyridamole for at least two days prior to regadenoson injection administration. Please see accompanying full Prescribing Information for Regadenoson Injection. This release includes forward-looking statements concerning Norepinephrine Bitartrate in 5% Dextrose Injection, Vasopressin in 0.9% Sodium Chloride Injection, Vancomycin Injection, USP in 5% Dextrose, Ropivacaine Hydrochloride Injection, USP and Regadenoson Injection pre-filled syringe, including potential benefits associated with the use of these products. 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: demand for and market acceptance for new and existing products; product development risks; inability to create additional production capacity in a timely manner or the occurrence of other manufacturing or supply difficulties (including as a result of natural disasters, public health crises and epidemics/pandemics, regulatory actions or otherwise); satisfaction of regulatory and other requirements; actions of regulatory bodies and other governmental authorities; product quality, manufacturing or supply, or patient safety issues; changes in law and regulations; and other risks identified in Baxter's most recent filing on Form 10-K and Form 10-Q and other SEC filings, all of which are available on Baxter's website. Baxter does not undertake to update its forward-looking statements. Baxter is a registered trademark of Baxter International Inc. 1 Baxter data on > 2 Mercaldi CJ, Lanes S, Bradt J. Comparative risk of bloodstream infection in hospitalized patients receiving intravenous medication by open, point-of-care, or closed delivery systems. Am J Health-Syst Pharm. 2013;70:957-965. 3 Billstein-Leber M, Carrillo CJD, Cassano AT, Moline K, Robertson JJ. ASHP Guidelines on Preventing Medication Errors in Hospitals. Am J Health Syst Pharm. 2018;75(19):1493-1517. US-PH57-240005 (v1.0) 04/2024 View source version on businesswire.com: Contacts Media Contact Andrea Johnson, (224) 948-5353 media@baxter.com Investor Contact Clare Trachtman, (224) 948-3020 Source: Baxter International Inc. View this news release online at: