Dopamine hydrochloride

PK modeling data provide insights into potential dosing conversions and strategies for switching to UZEDY from a long-acting injectable (LAI) formulation of risperidone microspheres (R064766) Additional UZEDY data include a new analysis from the Phase 3 RISE trial reinforcing its efficacy and safety profile in adults with schizophrenia ADVANCE, a global survey study, will also provide real-world findings on LAI utilization from healthcare professionals, caregivers and patients TEL AVIV, Israel & PARSIPPANY, N.J.--(BUSINESS WIRE)-- Teva Pharmaceuticals, a U.S. affiliate of Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA), today announced the presentation of eight studies from its LAI schizophrenia research program, including data evaluating UZEDY, an extended-release injectable suspension of risperidone for subcutaneous use every one or two months for the treatment of schizophrenia in adults. The data were presented at the 2024 Congress of the Schizophrenia International Research Society (SIRS) taking place from April 3-7, 2024 in Florence, Italy. “As part of Teva’s commitment to advancing treatment innovation for schizophrenia patients, this research provides clinical insights into how healthcare providers may switch appropriate patients to UZEDY, a subcutaneous risperidone LAI option with flexible dosing,” said Eric Hughes, MD, Ph.D, Executive Vice President of Global R&D and Chief Medical Officer at Teva. “Schizophrenia is a complex mental health condition where the treatment needs and preferences of those living with it may evolve over time. These data collectively demonstrate the efficacy and safety profile of UZEDY – reinforcing its potential as a treatment option that may help lower rates of relapse and hospitalization.” Presented data include population pharmacokinetic (PopPK) modeling to investigate dosing conversion strategies for switching patients to a once-monthly or once every two-months subcutaneous dose of UZEDY from a biweekly intramuscular LAI formulation of risperidone microspheres (R064766). The analysis aims to address the knowledge gap as limited clinical data currently exist on optimal strategies for switching between the various available LAI treatment options, which have differing pharmacokinetic (PK) properties. In the PopPK analysis, patient model simulations showed that switching to UZEDY at 4-6 weeks after the last dose of R064766 provided comparable PK exposures by the second dose. Specifically, switching patients to UZEDY 5 weeks after the last dose of R064766 achieved PK exposures similar to those achieved with R064766 at a steady state. The optimal switching strategy should be determined by clinicians on an individual basis, considering factors such as patient preference, scheduling convenience, and potential tolerability issues or risk of symptom breakthrough. Additional key data being presented at the SIRS Annual Meeting include: New data from RISE (Risperidone Subcutaneous Extended-Release Study), the Phase 3 pivotal trial that supported the FDA approval of UZEDY. An analysis estimated the number needed to treat (NNT) and the number needed to harm (NNH), clinically relevant measures that help provide healthcare providers with an understanding of the benefits and risks of UZEDY and inform clinical decision-making. Qualitative data from two ADVANCE (Attitudes Driving Regional Differences in LAI Antipsychotic Utilization for Schizophrenia Among Healthcare Professionals, Patients, and Caregivers) surveys: In the healthcare provider survey, ten psychiatrists (spending an average of 45% of their time at hospital-based outpatient clinics) and seven psychiatric nurses (averaging 47% of time at community mental health centers) were interviewed. Findings suggest that regional differences in LAI utilization rates are likely influenced by a combination of factors, including systemic, HCP, and patient factors. In the patient survey, approximately 20 patients and 19 caregivers completed a 60-minute interview regarding the use of LAIs in schizophrenia. Unfavorable early experiences, especially in the inpatient setting, can negatively impact patients’ perception of and willingness to accept LAIs. The survey findings offer further key insights into addressing global adherence and inconsistent utilization challenges with LAIs. Below is the full set of data presented by Teva at SIRS 2024. AUSTEDO ® XR (deutetrabenazine): (Encore) Occupational Impact of Tardive Dyskinesia (TD): a Cross-Sectional, International Survey Assessing the Perceptions and Experiences of Patients With TD and Physicians Who Treat TD (Encore) Burden and Management of Tardive Dyskinesia (TD): A Cross-Sectional, International Survey Study to Assess the Perceptions and Experiences of Physicians and Patients With TD (De novo) Patient and Caregiver Experiences With Tardive Dyskinesia: Emotions, Challenges, and Unmet Needs in the Patient Journey UZEDY (risperidone): (De novo) Switching Patients With Schizophrenia to TV-46000, a Long-Acting Subcutaneous Antipsychotic (LASCA), From Risperidone Microspheres (R064766): An Exploration of Population Pharmacokinetic (PopPK)–Based Strategies (De novo) Clinical Benefit and Risk Profile of TV-46000 for Patients With Schizophrenia as Assessed by Number Needed to Treat (NNT) and Number Needed to Harm (NNH) TV-44749 (olanzapine): (De novo) TV-44749, a Long-Acting Subcutaneous (sc) Injectable Formulation of Olanzapine is Designed to Provide Sustained Controlled Concentrations and to Eliminate the Causes of Post-Injection delirium/sedation Syndrome (PDSS) (De novo) Population Pharmacokinetic Modeling Following Administration of Olanzapine for Extended-Release Injectable Suspension (TV-44749) for Subcutaneous Use to Support Dose Selection for Phase 3 Clinical Trial (SOLARIS) LAI Real-World Insights: (De novo) Attitudes DriVing regional differences in LAI ANtipsychotic utilization for schizophrenia among healthcare professionals, patients, and CaregivErs (ADVANCE): healthcare professional qualitative interviews (De novo) Attitudes DriVing regional differences in LAI ANtipsychotic utilization for schizophrenia among healthcare professionals, patients, and CaregivErs (ADVANCE): patient and caregiver qualitative interviews (De novo) Initiation Regimens for Long-Acting Injectable Antipsychotics Requiring Oral Supplementation: Impact on Subsequent Maintenance Treatment Adherence and Persistence INDICATION AND USAGE UZEDY (risperidone) extended-release injectable suspension for subcutaneous use is indicated for the treatment of schizophrenia in adults. WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. UZEDY is not approved for use in patients with dementia-related psychosis and has not been studied in this patient population. See below for additional Important Safety Information. TV-44749 (olanzapine) is an investigational extended-release injectable suspension for subcutaneous use and is not approved by any regulatory authority for any use and its safety and efficacy are not established. About Schizophrenia Schizophrenia is a chronic, progressive and severely debilitating mental disorder that affects how one thinks, feels and acts. 1 Patients experience an array of symptoms, which may include delusions, hallucinations, disorganized speech or behavior and impaired cognitive ability. 1,2,3 Approximately 1% of the world’s population will develop schizophrenia in their lifetime, and 3.5 million people in the U.S. are currently diagnosed with the condition. 2,3 Although schizophrenia can occur at any age, the average age of onset tends to be in the late teens to the early 20s for men, and the late 20s to early 30s for women. 3 The long-term course of schizophrenia is marked by episodes of partial or full remission broken by relapses that often occur in the context of psychiatric emergency and require hospitalization. 3 Approximately 80% of patients experience multiple relapses over the first five years of treatment, and each relapse carries a biological risk of loss of function, treatment refractoriness, and changes in brain morphology. 4,5,6 Patients are often unaware of their illness and its consequences, contributing to treatment nonadherence, high discontinuation rates, and ultimately, significant direct and indirect healthcare costs from subsequent relapses and hospitalizations. 1,2,3,4,5,6 About UZEDY UZEDY (risperidone) extended-release injectable suspension, for subcutaneous use, is indicated for the treatment of schizophrenia in adults. In clinical trials, UZEDY significantly reduced the risk of schizophrenia relapse. 7,8 UZEDY administers risperidone through copolymer technology under license from MedinCell that allows for absorption and sustained release after subcutaneous injection. UZEDY is the only long-acting, subcutaneous formulation of risperidone available in both one- and two-month dosing intervals. 7 For full prescribing information, visit https://www.uzedy.com/globalassets/uzedy/prescribing-information.pdf . IMPORTANT SAFETY INFORMATION CONTINUED CONTRAINDICATIONS: UZEDY is contraindicated in patients with a known hypersensitivity to risperidone, its metabolite, paliperidone, or to any of its components. Hypersensitivity reactions, including anaphylactic reactions and angioedema, have been reported in patients treated with risperidone or paliperidone. WARNINGS AND PRECAUTIONS Cerebrovascular Adverse Reactions: In trials of elderly patients with dementia-related psychosis, there was a significantly higher incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatalities, in patients treated with oral risperidone compared to placebo. UZEDY is not approved for use in patients with dementia-related psychosis. Neuroleptic Malignant Syndrome (NMS): NMS, a potentially fatal symptom complex, has been reported in association with antipsychotic drugs. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status including delirium, and autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. If NMS is suspected, immediately discontinue UZEDY and provide symptomatic treatment and monitoring. Tardive Dyskinesia (TD): TD, a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements, may develop in patients treated with antipsychotic drugs. Although the prevalence of the syndrome appears to be highest among the elderly, especially elderly women, it is impossible to predict which patients will develop the syndrome. Whether antipsychotic drug products differ in their potential to cause TD is unknown. The risk of developing TD and the likelihood that it will become irreversible are believed to increase with the duration of treatment and the cumulative dose. The syndrome can develop, after relatively brief treatment periods, even at low doses. It may also occur after discontinuation. TD may remit, partially or completely, if antipsychotic treatment is discontinued. Antipsychotic treatment, itself, however, may suppress (or partially suppress) the signs and symptoms of the syndrome, possibly masking the underlying process. The effect that symptomatic suppression has upon the long-term course of the syndrome is unknown. If signs and symptoms of TD appear in a patient treated with UZEDY, drug discontinuation should be considered. However, some patients may require treatment with UZEDY despite the presence of the syndrome. In patients who do require chronic treatment, use the lowest dose and the shortest duration of treatment producing a satisfactory clinical response. Periodically reassess the need for continued treatment. Metabolic Changes: Atypical antipsychotic drugs have been associated with metabolic changes that may increase cardiovascular/cerebrovascular risk. These metabolic changes include hyperglycemia, dyslipidemia, and body weight gain. While all of the drugs in the class have been shown to produce some metabolic changes, each drug has its own specific risk profile. Hyperglycemia and diabetes mellitus (DM), in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, have been reported in patients treated with atypical antipsychotics, including risperidone. Patients with an established diagnosis of DM who are started on atypical antipsychotics, including UZEDY, should be monitored regularly for worsening of glucose control. Patients with risk factors for DM (e.g., obesity, family history of diabetes) who are starting treatment with atypical antipsychotics, including UZEDY, should undergo fasting blood glucose (FBG) testing at the beginning of treatment and periodically during treatment. Any patient treated with atypical antipsychotics, including UZEDY, should be monitored for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Patients who develop symptoms of hyperglycemia during treatment with atypical antipsychotics, including UZEDY, should undergo FBG testing. In some cases, hyperglycemia has resolved when the atypical antipsychotic, including risperidone, was discontinued; however, some patients required continuation of antidiabetic treatment despite discontinuation of risperidone. Dyslipidemia has been observed in patients treated with atypical antipsychotics. Weight gain has been observed with atypical antipsychotic use. Monitoring weight is recommended. Hyperprolactinemia: As with other drugs that antagonize dopamine D 2 receptors, risperidone elevates prolactin levels and the elevation persists during chronic administration. Risperidone is associated with higher levels of prolactin elevation than other antipsychotic agents. Orthostatic Hypotension and Syncope: UZEDY may induce orthostatic hypotension associated with dizziness, tachycardia, and in some patients, syncope. UZEDY should be used with particular caution in patients with known cardiovascular disease, cerebrovascular disease, and conditions which would predispose patients to hypotension and in the elderly and patients with renal or hepatic impairment. Monitoring of orthostatic vital signs should be considered in all such patients, and a dose reduction should be considered if hypotension occurs. Clinically significant hypotension has been observed with concomitant use of oral risperidone and antihypertensive medication. Falls: Antipsychotics, including UZEDY, may cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls and, consequently, fractures or other fall-related injuries. Somnolence, postural hypotension, motor and sensory instability have been reported with the use of risperidone. For patients, particularly the elderly, with diseases, conditions, or medications that could exacerbate these effects, assess the risk of falls when initiating antipsychotic treatment and recurrently for patients on long-term antipsychotic therapy. Leukopenia, Neutropenia, and Agranulocytosis have been reported with antipsychotic agents, including risperidone. In patients with a pre-existing history of a clinically significant low white blood cell count (WBC) or absolute neutrophil count (ANC) or a history of drug-induced leukopenia or neutropenia, perform a complete blood count (CBC) frequently during the first few months of therapy. In such patients, consider discontinuation of UZEDY at the first sign of a clinically significant decline in WBC in the absence of other causative factors. Monitor patients with clinically significant neutropenia for fever or other symptoms or signs of infection and treat promptly if such symptoms or signs occur. Discontinue UZEDY in patients with ANC < 1000/mm 3 ) and follow their WBC until recovery. Potential for Cognitive and Motor Impairment: UZEDY, like other antipsychotics, may cause somnolence and has the potential to impair judgement, thinking, and motor skills. Somnolence was a commonly reported adverse reaction associated with oral risperidone treatment. Caution patients about operating hazardous machinery, including motor vehicles, until they are reasonably certain that treatment with UZEDY does not affect them adversely. Seizures: During premarketing studies of oral risperidone in adult patients with schizophrenia, seizures occurred in 0.3% of patients (9 out of 2,607 patients), two in association with hyponatremia. Use UZEDY cautiously in patients with a history of seizures or other conditions that potentially lower the seizure threshold. Dysphagia: Esophageal dysmotility and aspiration have been associated with antipsychotic drug use. Antipsychotic drugs, including UZEDY, should be used cautiously in patients at risk for aspiration. Priapism has been reported during postmarketing surveillance for other risperidone products. A case of priapism was reported in premarket studies of UZEDY. Severe priapism may require surgical intervention. Body temperature regulation . Disruption of the body’s ability to reduce core body temperature has been attributed to antipsychotic agents. Both hyperthermia and hypothermia have been reported in association with oral risperidone use. Strenuous exercise, exposure to extreme heat, dehydration, and anticholinergic medications may contribute to an elevation in core body temperature; use UZEDY with caution in patients who experience these conditions. ADVERSE REACTIONS The most common adverse reactions with risperidone (≥5% and greater than placebo) were parkinsonism, akathisia, dystonia, tremor, sedation, dizziness, anxiety, blurred vision, nausea, vomiting, upper abdominal pain, stomach discomfort, dyspepsia, diarrhea, salivary hypersecretion, constipation, dry mouth, increased appetite, increased weight, fatigue, rash, nasal congestion, upper respiratory tract infection, nasopharyngitis, and pharyngolaryngeal pain. The most common injection site reactions with UZEDY (≥5% and greater than placebo) were pruritus and nodule. DRUG INTERACTIONS Carbamazepine and other strong CYP3A4 inducers decrease plasma concentrations of risperidone. Fluoxetine, paroxetine, and other strong CYP2D6 inhibitors increase risperidone plasma concentration. Due to additive pharmacologic effects, the concomitant use of centrally-acting drugs, including alcohol, may increase nervous system disorders. UZEDY may enhance the hypotensive effects of other therapeutic agents with this potential. UZEDY may antagonize the pharmacologic effects of dopamine agonists. Concomitant use with methylphenidate, when there is change in dosage of either medication, may increase the risk of extrapyramidal symptoms (EPS) USE IN SPECIFIC POPULATIONS Pregnancy: May cause EPS and/or withdrawal symptoms in neonates with third trimester exposure. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including UZEDY, during pregnancy. Healthcare providers are encouraged to register patients by contacting the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or online at http://womensmentalhealth.org/clinicaland-research-programs/pregnancyregistry/ . Lactation: Infants exposed to risperidone through breastmilk should be monitored for excess sedation, failure to thrive, jitteriness, and EPS. Fertility: UZEDY may cause a reversible reduction in fertility in females. Pediatric Use: Safety and effectiveness of UZEDY have not been established in pediatric patients. Renal or Hepatic Impairment: Carefully titrate on oral risperidone up to at least 2 mg daily before initiating treatment with UZEDY. Patients with Parkinson’s disease or dementia with Lewy bodies can experience increased sensitivity to UZEDY. Manifestations and features are consistent with NMS. Please see the full Prescribing Information for UZEDY, including Boxed WARNING. About AUSTEDO ® XR Extended-Release Tablets and AUSTEDO ® Tablets AUSTEDO XR and AUSTEDO are the first vesicular monoamine transporter 2 (VMAT2) inhibitors approved by the U.S. Food and Drug Administration in adults for the treatment of tardive dyskinesia and for the treatment of chorea associated with Huntington’s disease. Safety and effectiveness in pediatric patients have not been established. AUSTEDO XR is the once-daily formulation of AUSTEDO. INDICATIONS AND USAGE AUSTEDO ® XR (deutetrabenazine) extended-release tablets and AUSTEDO ® (deutetrabenazine) tablets are indicated in adults for the treatment of chorea associated with Huntington’s disease and for the treatment of tardive dyskinesia. IMPORTANT SAFETY INFORMATION Depression and Suicidality in Patients with Huntington’s Disease: AUSTEDO XR and AUSTEDO can increase the risk of depression and suicidal thoughts and behavior (suicidality) in patients with Huntington’s disease. Balance the risks of depression and suicidality with the clinical need for treatment of chorea . Closely monitor patients for the emergence or worsening of depression, suicidality, or unusual changes in behavior. Inform patients, their caregivers, and families of the risk of depression and suicidality and instruct them to report behaviors of concern promptly to the treating physician. Exercise caution when treating patients with a history of depression or prior suicide attempts or ideation. AUSTEDO XR and AUSTEDO are contraindicated in patients who are suicidal, and in patients with untreated or inadequately treated depression. Contraindications: AUSTEDO XR and AUSTEDO are contraindicated in patients with Huntington’s disease who are suicidal, or have untreated or inadequately treated depression. AUSTEDO XR and AUSTEDO are also contraindicated in: patients with hepatic impairment; patients taking reserpine or within 20 days of discontinuing reserpine; patients taking monoamine oxidase inhibitors (MAOIs), or within 14 days of discontinuing MAOI therapy; and patients taking tetrabenazine or valbenazine. Clinical Worsening and Adverse Events in Patients with Huntington’s Disease: AUSTEDO XR and AUSTEDO may cause a worsening in mood, cognition, rigidity, and functional capacity . Prescribers should periodically re-evaluate the need for AUSTEDO XR or AUSTEDO in their patients by assessing the effect on chorea and possible adverse effects. QTc Prolongation: AUSTEDO XR and AUSTEDO may prolong the QT interval, but the degree of QT prolongation is not clinically significant when AUSTEDO XR or AUSTEDO is administered within the recommended dosage range. AUSTEDO XR and AUSTEDO should be avoided in patients with congenital long QT syndrome and in patients with a history of cardiac arrhythmias. Neuroleptic Malignant Syndrome (NMS), a potentially fatal symptom complex reported in association with drugs that reduce dopaminergic transmission, has been observed in patients receiving tetrabenazine. The risk may be increased by concomitant use of dopamine antagonists or antipsychotics. The management of NMS should include immediate discontinuation of AUSTEDO XR and AUSTEDO; intensive symptomatic treatment and medical monitoring; and treatment of any concomitant serious medical problems. Akathisia, Agitation, and Restlessness: AUSTEDO XR and AUSTEDO may increase the risk of akathisia, agitation, and restlessness. The risk of akathisia may be increased by concomitant use of dopamine antagonists or antipsychotics. If a patient develops akathisia, the AUSTEDO XR or AUSTEDO dose should be reduced; some patients may require discontinuation of therapy. Parkinsonism: AUSTEDO XR and AUSTEDO may cause parkinsonism in patients with Huntington’s disease or tardive dyskinesia. Parkinsonism has also been observed with other VMAT2 inhibitors. The risk of parkinsonism may be increased by concomitant use of dopamine antagonists or antipsychotics. If a patient develops parkinsonism, the AUSTEDO XR or AUSTEDO dose should be reduced; some patients may require discontinuation of therapy. Sedation and Somnolence: Sedation is a common dose-limiting adverse reaction of AUSTEDO XR and AUSTEDO. Patients should not perform activities requiring mental alertness, such as operating a motor vehicle or hazardous machinery, until they are on a maintenance dose of AUSTEDO XR or AUSTEDO and know how the drug affects them. Concomitant use of alcohol or other sedating drugs may have additive effects and worsen sedation and somnolence. Hyperprolactinemia: Tetrabenazine elevates serum prolactin concentrations in humans. If there is a clinical suspicion of symptomatic hyperprolactinemia, appropriate laboratory testing should be done and consideration should be given to discontinuation of AUSTEDO XR and AUSTEDO. Binding to Melanin-Containing Tissues: Deutetrabenazine or its metabolites bind to melanin-containing tissues and could accumulate in these tissues over time. Prescribers should be aware of the possibility of long-term ophthalmologic effects . Common Adverse Reactions: The most common adverse reactions for AUSTEDO (>8% and greater than placebo) in a controlled clinical study in patients with Huntington’s disease were somnolence, diarrhea, dry mouth, and fatigue. The most common adverse reactions for AUSTEDO (4% and greater than placebo) in controlled clinical studies in patients with tardive dyskinesia were nasopharyngitis and insomnia. Adverse reactions with AUSTEDO XR extended-release tablets are expected to be similar to AUSTEDO tablets. Please see accompanying full Prescribing Information , including Boxed Warning. About Teva Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) is a global pharmaceutical leader with a category-defying portfolio, harnessing our generics expertise and stepping up innovation to continue the momentum behind the discovery, delivery, and expanded development of modern medicine. For over 120 years, Teva’s commitment to bettering health has never wavered. Today, the company’s global network of capabilities enables its 37,000 employees across 58 markets to push the boundaries of scientific innovation and deliver quality medicines to help improve health outcomes of millions of patients every day. To learn more about how Teva is all in for better health, visit www.tevapharm.com . Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, which are based on management’s current beliefs and expectations and are subject to substantial risks and uncertainties, both known and unknown, that could cause our future results, performance or achievements to differ significantly from that expressed or implied by such forward-looking statements. You can identify these forward-looking statements by the use of words such as “should,” “expect,” “anticipate,” “estimate,” “target,” “may,” “project,” “guidance,” “intend,” “plan,” “believe” and other words and terms of similar meaning and expression in connection with any discussion of future operating or financial performance. Important factors that could cause or contribute to such differences include risks relating to: our ability to successfully develop and commercialize UZEDY; our ability to successfully develop and commercialize AUSTEDO XR; our ability to develop and obtain regulatory approvals to our late-stage pipeline assets, including olanzapine LAI (TEV-‘749); our ability to successfully execute our Pivot to Growth strategy, including to expand our innovative and biosimilar medicines pipeline and profitably commercialize the innovative medicines and biosimilar portfolio, whether organically or through business development; and other factors discussed in this press release, and in our Annual Report on Form 10-K for the year ended December 31, 2023, including in the sections captioned "Risk Factors.” Forward-looking statements speak only as of the date on which they are made, and we assume no obligation to update or revise any forward-looking statements or other information contained herein, whether as a result of new information, future events or otherwise. You are cautioned not to put undue reliance on these forward-looking statements. ________________________ 1 Substance Abuse and Mental Health Services Administration. Schizophrenia. https://www.samhsa.gov/mental-health/schizophrenia . Accessed November 2023. 2 Velligan DI, Rao S. The epidemiology and global burden of schizophrenia. J Clin Psychiatry. 2023;84(1):MS21078COM5. https://doi.org/10.4088/JCP.MS21078COM5 . 3 Wander C. (2020). Schizophrenia: opportunities to improve outcomes and reduce economic burden through managed care. The American journal of managed care, 26(3 Suppl), S62–S68. https://doi.org/10.37765/ajmc.2020.43013 4 Emsley, R., & Kilian, S. (2018). Efficacy and safety profile of paliperidone palmitate injections in the management of patients with schizophrenia: an evidence-based review. Neuropsychiatric disease and treatment, 14, 205–223. 5 Emsley, R., Chiliza, B., Asmal, L. et al. (2013) The nature of relapse in schizophrenia. BMC Psychiatry 13, 50. 6 Andreasen, N. C., et al. (2013). Relapse duration, treatment intensity, and brain tissue loss in schizophrenia: a prospective longitudinal MRI study. The American journal of psychiatry, 170(6), 609–615. 7 UZEDY™ (risperidone) extended-release injectable suspension, for subcutaneous injection Current Prescribing Information. Parsippany, NJ. Teva Neuroscience, Inc. 8 Data on file. Parsippany, NJ: Teva Neuroscience, Inc. View source version on businesswire.com : https://www.businesswire.com/news/home/20240406098130/en/ IR Ran Meir +1 (267) 468-4475 Yael Ashman +972 (3) 914 8262 Sanjeev Sharma +1 (973) 658 2700 PR Kelley Dougherty +1 (973) 832-2810 Eden Klein +972 (3) 906 2645 Source: Teva Pharmaceutical Industries Limited

精彩内容近年来，国家及地方省市大力开展短缺药“保供稳价”工作：上海定期公布部分短缺药全国平均价，符合价格低、急（抢）救、妇儿专科、注射剂等特征的品种备受关注；国家发文推进短缺药带量采购落地执行，广东、重庆、河南等多个省联盟集采先行试点，去甲肾上腺素、间羟胺......超10亿大品种频频上榜，华润、白云山、科伦等国内制药巨头强势突围。政策助力，为短缺药“保供稳价”自2018年4+7集采以来，国采或地方集采中，中选药生产厂商因断供、停产问题，而被取消集采资格的情况时有发生。加上近年新冠疫情冲击，经济仍处复苏阶段，部分企业因原料药价格上涨，工厂停产或减产、生产线等问题，产品无法正常生产而导致断供的情况也不计其数。为应对药品供应短缺，及时对市面上短缺药进行动态监控及调整，国家卫健委于2020年12月印发了《国家短缺药品清单》，重点针对6个国家短缺药和57个国家临床必需易短缺药，通过监测掌握药品供应和使用情况，及早预警，及时采取措施，以防止短缺情况发生。随后，多项相关保障短缺药供应的举措密集出台。如：自2021年起，国家卫健委定期公布“短缺药品保供稳价工作”执行情况，旨在从多方面持续完善制度设计、落实工作举措、提升保供能力，助力解决短缺药品供应保障等问题。国家卫健委公布的“短缺药品保供稳价工作”情况来源：国家卫健委官网，米内网整理不难发现，对于短缺药的保供稳价，国家也是铆足干劲，持续完善多部门药品信息协同监测机制，多维度提升药品的供应水平，加强重点药品的供应与监测。获批企业过百家，药品短缺的根本何在？2024年3月，国家卫健委公布了最新的“短缺药保供稳价近期工作情况”，其中提及：全链条保障短缺药稳定供应；加快推进短缺药审评审批；探索开展短缺药集中带量采购；工信部会同4部门联合印发《关于加强短缺药品和国家组织药品集中采购中选药品生产储备监测工作的通知》（下文简称《通知》），积极建立中央和地方两级常态短缺药储备，进一步加强监测预警，及时研判生产供应短缺风险。来源：国家卫健委官网《通知》内容明确，要求将对109个短缺药制剂、60个短缺药原料药以及240个国采中选药的生产企业进行生产储备监测，监测企业目录实施动态调整。109个易短缺药物（制剂）名单来源：工信部官网，米内网整理事实上，该名单是由国家早前发布《国家短缺药品清单》及《国家临床必需易短缺药品清单》品种进一步细分为109个制剂，其中注射剂占比接近90%。经查询发现，部分产品获批企业数多则上百家，但在临床供应上依然短缺，原因到底为何？比如葡萄糖酸钙，适用于治疗钙缺乏，急性血钙过低、碱中毒及甲状旁腺功能低下所致的手足搐搦症等。作为临床常用的钙补充剂，2022年该药在中国城市公立医院、县级公立医院、城市社区中心及乡镇卫生院（简称中国公立医疗机构）终端销售额超过7亿元；其中，注射剂市占比超九成，获批生产葡萄糖酸钙注射液的企业多达62家。2022年中国公立医疗机构终端葡萄糖酸钙剂型格局来源：米内网中国公立医疗机构药品终端竞争格局然而，葡萄糖酸钙注射液临床供应仍存在短缺，这或与部分原料药企业对销售市场的垄断密不可分。2020年初，国家市场监督管理总局对3家葡萄糖酸钙原料药经销企业垄断行为作出行政处罚，共计罚没3.25亿元。通过市场整顿后，该药品的供应及价格虽逐步恢复正常，但此前造成的影响仍需时间“修补”。尿激酶为溶栓药，主要用于血栓栓塞性疾病的溶栓治疗，是一种临床急（抢）救短缺药。米内网数据显示，目前注射用尿激酶有30家企业拥有生产批文，2022年在中国公立医疗机构终端销售额突破10亿元，同比增长18.96%，南大药业、人福药业、丰原制药均以两位数的市场份额领跑。近年来中国公立医疗机构终端尿激酶销售趋势（单位：万元）来源：米内网中国公立医疗机构药品终端竞争格局对于一款企业竞争格局充分、获取途径便利（尿激酶从人体尿液中提取）的潜力品种，为何临床上频频出现短缺？究其原因，主要是人们对环境的要求越来越高，允许尿液收集的场所却日趋减少，尿液的收集难度不断增大，导致原料药制备成本提高，企业生产的意愿明显下降，产品出现短缺的情况显然在所难免。此外，甘露醇注射液、硫酸阿托品注射液获批生产的企业数即便高达143家和97家，但也因原料药供应不足或价格过高等出现短缺。可见，原料药短缺或价格上涨俨然成为企业制剂生产中难以逾越的一座高山。价格低、急（抢）救、妇儿专科......短缺药频频“上榜”2022年6月至今，上海阳光医药采购网先后公示了多批短缺药的全国平均价，以供各医疗机构根据市场供需情况，在保供稳价的基础上，采购质量可靠、价格适宜的药品。来源：上海阳光医药采购网据不完全统计，2023年1月至2024年1月，共有24款短缺药的全国平均价拟公示，其中“上榜”次数最多的品种依次为：硫酸镁注射液（5次）、地西泮注射液（4次）和盐酸肾上腺素注射液（4次）；按治疗大类统计，心脑血管系统药物数量最多，有11个品种入围，其次为神经系统药物（3个）、抗肿瘤和免疫调节剂（3个）等。2023年1月-2024年1月部分短缺药全国平均价情况来源：上海阳光医药采购网，米内网整理硫酸镁注射液为抗早产药物，常用于妊娠高血压，治疗先兆子痫和子痫等。在中国公立医疗机构终端，该药近年销售额保持稳定增长，2020-2022年均在2亿元以上，2023年上半年同比上涨1.94%。在上海历次公布的全国平均价中，硫酸镁注射液（10ml:2.5g）全国平均单价在4.6-5.4元/支之间。整体而言，该药基本符合价格低、急（抢）救、妇儿专科、注射剂等产品特征。地西泮注射液、盐酸肾上腺素注射液分别为抗癫痫注射用首选药和心肺复苏急（抢）救用药，其2023年上半年在中国公立医疗机构终端销售增速均超20%。翻看上海公开的全国平均价数据，上述两款产品全国平均单价均在10元/支以下，也与价格低、急（抢）救、注射剂等短缺药的特征基本符合。2款短缺药在中国公立医疗机构终端的销售增速来源：米内网中国公立医疗机构药品终端竞争格局除此之外，多次“上榜”的硝酸甘油注射液、注射用盐酸多巴胺、注射用氢化可的松琥珀酸钠等短缺药也大多满足“价格低、急（抢）救、妇儿专科、注射剂”四大基本特征。短缺药集采加速推进，40余个品种先行试点2023年初，国家医保局发文明确，重点指导开展易短缺和急（抢）救药省际联盟采购；2024年3月，国家卫健委在工作报告中指出，将继续探索开展短缺药品集中带量采购......在国家指导文件的驱动下，多个短缺药省际联盟集采应运而生。来源：重庆市医保局官网2024年2月，重庆等10省（市、自治区）组成的常用药和短缺药联盟集采拉开序幕。20个拟纳入集采的短缺药中，包括促皮质素注射剂、硫代硫酸钠注射剂、新斯的明注射剂等2023年上半年在中国公立医疗机构终端销售增速均达两位数的潜力品种，涉及重庆药友制药、上药新亚药业、苑东生物等知名药企。来源：广州药品集团采购平台2023年12月，广东牵头的28省易短缺和急（抢）救药联盟集采完满收官。17个易短缺和急（抢）救药品种竞价成功，中选产品既有去甲肾上腺素注射剂、间羟胺注射剂等2022年在中国公立医疗机构终端销售额均超10亿元的大品种，也有酚妥拉明注射剂、洛贝林注射剂等临床必需但较为小众的“小品种”，上海禾丰制药、天津金耀药业各以6个和5个中选产品在数量上领跑。通过此次竞价集采，近三年挂网价格累计涨幅超过1倍的7个品种和超过10倍以上的2个品种，价格有望重回合理水平，市场价格无序飙升等情况将得到有效遏制。预计联盟内省区每年可节约费用约50亿元。来源：河南省医保局官网2023年10月，河南等19省药品联盟集采结果出炉。23个采购成功的品种中，不乏甘露醇注射剂、凝血酶散剂、硝酸甘油注射剂等被纳入国家短缺药目录的品种，其2022年在中国公立医疗机构终端销售规模分别超10亿元、7亿元和4亿元，中选企业涉及华润医药、白云山明兴制药、科伦药业、石家庄四药等国内制药巨头。结语随着短缺药品供应保障体系逐步健全，以及集中带量采购工作稳步推进，我国药品短缺矛盾和药价无序飙升等情况得到进一步缓解，短缺药“保供稳价”成绩初见成效。但由于短缺药的供应受临床用药需求或不确定因素的影响，国家已着重对药品生产供应、药品不良反应、药品持有人制度、药品价格及成本、过评后挂网价格等进行全方位监测和动态调整，不断完善省级药品联动挂网和储备机制，力求更高效地解决短缺药供应不足等问题。来源：米内网数据库、国家卫健委等注：米内网《中国公立医疗机构药品终端竞争格局》，统计范围是：中国城市公立医院、县级公立医院、城市社区中心以及乡镇卫生院，不含民营医院、私人诊所、村卫生室；上述销售额以产品在终端的平均零售价计算。数据统计截至4月3日，如有疏漏，欢迎指正！本文为原创稿件，转载请注明来源和作者，否则将追究侵权责任。投稿及报料请发邮件到872470254@qq.com稿件要求详询米内微信首页菜单栏商务及内容合作可联系QQ：412539092【分享、点赞、在看】点一点不失联哦