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BRENTWOOD, Tenn., March 11, 2025 /PRNewswire/ -- Currax Pharmaceuticals LLC ("Currax"), a specialty pharmaceutical company and manufacturer of the #1 branded oral weight loss medication CONTRAVE® (naltrexone HCl/bupropion HCl), today announced the publication of its Cardiovascular Health Outcomes Analysis (HOA) for CONTRAVE®/MYSIMBA® in Obesity Pillars, the official journal of the Obesity Medicine Association. This peer-reviewed study, based on electronic health record data from more than 24,600 patients followed for over 4.7 years, found no evidence of excess cardiovascular risk and no statistically significant difference in major adverse cardiovascular events (MACE) between CONTRAVE/MYSIMBA and the comparator drug. The study's publication provides important real-world evidence that further substantiates the cardiovascular safety profile of CONTRAVE/MYSIMBA building on findings from prior clinical trials, a systemic literature review, two published FDA Adverse Event Reporting System (FAERS) database studies, and over ten years of post-marketing safety surveillance. These results provide valuable insights to support regulatory and clinical decision-making in the treatment of obesity. "The publication of this analysis in Obesity Pillars underscores the utility of evaluating long-term cardiovascular outcomes in routine clinical practice," said Michael Kyle, M.D., SVP, Chief Medical Officer of Currax Pharmaceuticals. "The findings further substantiate the cardiovascular safety profile of CONTRAVE/MYSIMBA, aligning with previous clinical and observational studies." CONTRAVE, approved in the U.S. and marketed in Europe as MYSIMBA, has been studied extensively in both randomized clinical trials and observational settings. The latest analysis builds upon prior research, including the LIGHT trial, and complements the ongoing INFORMUS trial, a large-scale cardiovascular outcomes study, which now has enrolled more than 3,000 patients and is designed to meet regulatory post-marketing requirements to further characterize long-term cardiovascular safety. "Obesity is a serious chronic disease, and it's critical that healthcare professionals have access to rigorous, data-driven evidence when considering treatment options," said George Hampton, President and CEO of Currax Pharmaceuticals. "Currax continues to invest in clinical trials designed to increase the utility of Contrave for physicians treating obesity." The full study is available in Obesity Pillars: About Currax Pharmaceuticals LLC Currax Pharmaceuticals LLC is a specialty pharmaceutical business focused on tackling the #1 and #2 causes of preventable death in the United States, smoking and obesity. Currax distributes a range of both branded and generic pharmaceutical products, including CONTRAVE® (naltrexone HCl/bupropion HCl), ONZETRA® Xsail® (sumatriptan nasal powder), Silenor® (doxepin), Treximet®, (sumatriptan/naproxen sodium), and the authorized generic of Treximet®. For more information, please visit . WHAT IS CONTRAVE? Along with diet and exercise, CONTRAVE is a prescription weight-loss medicine that may help some adults with a BMI > 30 kg/m2 (obese) or with a BMI of > 27 kg/m2 (overweight) with at least one weight-related medical problem such as high blood pressure, high cholesterol, or type 2 diabetes, lose weight and keep the weight off. It is not known if CONTRAVE changes your risk of heart problems or stroke or of death due to heart problems or stroke. It is not known if CONTRAVE is safe and effective when taken with other prescription, over-the-counter, or herbal weight-loss products. CONTRAVE is not approved to treat depression or other mental illnesses, or to help people quit smoking (smoking cessation). IMPORTANT SAFETY INFORMATION CONTRAVE can cause serious side effects including: Suicidal thoughts or actions: One of the ingredients in CONTRAVE is bupropion. Bupropion has caused some people to have suicidal thoughts or actions or unusual changes in behavior, whether or not they are taking medicines used to treat depression. Bupropion may increase the risk of suicidal thoughts or actions in some children, teenagers, and young adults within the first few months of treatment. If you already have depression or other mental illnesses, taking bupropion may cause it to get worse, especially within the first few months of treatment. While taking CONTRAVE, you or your family members should pay close attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings. This is very important when you start taking CONTRAVE or when your dose changes. Stop taking CONTRAVE and call a healthcare provider right away if you or your family members notice any of the following symptoms, especially if they are new, worse, or worry you: thoughts about suicide or dying; attempts to commit suicide; depression; anxiety; feeling agitated or restless; panic attacks; irritability; aggression, anger, or violence; acting on dangerous impulses; an extreme increase in activity and talking; other unusual changes in behavior or mood; trouble sleeping. CONTRAVE is not approved for use in children under the age of 18. Do not take CONTRAVE if you have uncontrolled high blood pressure; have or have had seizures; use other medicines that contain bupropion such as WELLBUTRIN, WELLBUTRIN SR, WELLBUTRIN XL, APLENZIN and ZYBAN; have or have had an eating disorder called anorexia or bulimia; are dependent on opioid pain medicines or use medicines to help stop taking opioids, or are in opiate withdrawal; drink a lot of alcohol and abruptly stop drinking, or use medicines called sedatives (these make you sleepy), benzodiazepines, or anti-seizure medicines and stop using them all of a sudden; are taking or have taken medicines called monoamine oxidase inhibitors (MAOIs) in the past 14 days; or are allergic to any of the ingredients in CONTRAVE. Tell your healthcare provider about all of your medical conditions including if you have: depression or other mental illnesses; attempted suicide; seizures; head injury; tumor or infection of brain or spine; low blood sugar or low sodium; liver or kidney problems; high blood pressure; heart attack, heart problems, or stroke; eating disorder; drinking a lot of alcohol; prescription medicine or street drug abuse; are 65 or older; diabetes; pregnant or planning to become pregnant; or breastfeeding. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. CONTRAVE may cause serious side effects, including: Seizures. There is a risk of having a seizure when you take CONTRAVE. The risk of seizure is higher in people who take higher doses of CONTRAVE, have certain medical conditions, or take CONTRAVE with certain other medicines. Do not take any other medicines while you are taking CONTRAVE unless your healthcare provider has said it is okay to take them. If you have a seizure while taking CONTRAVE, stop taking CONTRAVE and call your healthcare provider right away. Risk of opioid overdose. Do not take large amounts of opioids, including opioid-containing medicines, such as heroin or prescription pain pills, to try to overcome the opioid-blocking effects of naltrexone. This can lead to serious injury, coma, or death. Get emergency medical help right away if you take opioids and you: have trouble breathing become very drowsy with slowed breathing have slow, shallow breathing feel faint, very dizzy, confused, or have unusual symptoms Sudden opioid withdrawal. People who take CONTRAVE must not use any type of opioid including street drugs, prescription pain medicines, cough, cold, or diarrhea medicines that contain opioids, or opioid dependence treatments, for at least 7 to 10 days before starting CONTRAVE. Using opioids in the 7 to 10 days before you start taking CONTRAVE may cause you to suddenly have symptoms of opioid withdrawal when you take it. Sudden opioid withdrawal can be severe, and you may need to go to the hospital. Tell your healthcare provider you are taking CONTRAVE before a medical procedure or surgery. Severe allergic reactions. Stop taking CONTRAVE and call your healthcare provider or go to the nearest hospital emergency room right away if you have any of the following signs and symptoms of an allergic reaction: rash, itching, hives, fever, swollen lymph glands, painful sores in your mouth or around your eyes, swelling of your lips or tongue, chest pain, or trouble breathing. Increases in blood pressure or heart rate. Some people may get high blood pressure or have a higher heart rate when taking CONTRAVE. Your healthcare provider should check your blood pressure and heart rate before you start taking, and while you take CONTRAVE. Liver damage or hepatitis. Stop taking CONTRAVE and tell your healthcare provider if you have any of the following symptoms of liver problems: stomach area pain lasting more than a few days, dark urine, yellowing of the whites of your eyes, or tiredness. Your healthcare provider may need to stop treating you with CONTRAVE if you get signs or symptoms of a serious liver problem. Manic episodes. Bupropion can cause some people who were manic or depressed in the past to become manic or depressed again. Visual problems (angle-closure glaucoma). Signs and symptoms may include: eye pain, changes in vision, swelling or redness in or around the eye. Talk with your healthcare provider to find out if you are at risk for angle-closure glaucoma and to get treatment to prevent it if you are at risk. Increased risk of low blood sugar in people with type 2 diabetes mellitus who also take medicines to treat their diabetes (such as insulin or sulfonylureas). You should check your blood sugar before you start taking CONTRAVE and while you take CONTRAVE. The most common side effects of CONTRAVE include nausea, constipation, headache, vomiting, dizziness, trouble sleeping, dry mouth, and diarrhea. These are not all of the possible side effects of CONTRAVE. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit or call 1-800-FDA-1088. Please see the Full Prescribing Information, including Medication Guide, for CONTRAVE. Media Contact [email protected] SOURCE Currax Pharmaceuticals LLC WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

前  言 在职业环境中，为了保护工人免受有害物质的损害，需要根据职业接触限值（OEL）来设定合适的暴露水平。目前全球市售化学品约十万种，但是制订有OEL的化学物质只有1400多种，法定OEL制订是非常严谨的，因此制订速度远比不上化学品上市速度。本文将以制药行业为例，介绍高活性药物OEL的计算方法以及其中涉及的不确定度因子，旨在帮助企业制订公司内部的OEL，用于OEB分级等。 制药行业在药物生产过程中会涉及到活性药物成分（API，原料药），活性成分（AI）以及可分离中间体（IPI）。这些物质可能具有一定活性、毒性、致敏性和致畸性，其OEL通常低于1mg/m3，或尚未有公开可信的接触限值。制药企业需要根据活性药物成分所处的各个阶段，如药物发现和研究阶段、临床前研究阶段和临床研究阶段，确定数据的来源和详实程度。 通常临床前研究阶段前期，毒性数据是有限的，一般采取较为保守的OEL取值，可通过作用机制（Mechanism of action）、类似结构或原理的药物、交叉参照（Read cross 方法）、默认原则等方法来确定。在临床前研究阶段后期和临床实验阶段，将获得更多的毒性数据，通过一定流程可得到某个物质相对精确的OEL 或OEB。总之毒性数据越丰富，制订的OEL以及OEB越准确。 OEL制订 原料药的OEL可以按照以下公式进行计算： NOAEL: 无可见有害作用水平，有些资料也有用NOEL (未观察到效应水平) 来计算。 BW: 成年人体重，一般取值范围为50~70kg V: 8小时吸入的空气量，一般取值为10m3 S: 血浆稳态浓度天数（天），一般取值为1 UF: 不确定因子，数据来源为急性到慢性的外推（10倍），药物致癌致敏致畸（10倍），利用LOAEL估算NOAEL(10倍)，利用动物数据到人类数据的外推（10倍） α：吸入吸收率（%），一般取1。 其实整个计算的难度还是UF的确定。不确定因子的取值，在不同的标准和资料有所区别。我们主要引用了OHTA的《Occupational Hygiene in the Pharmaceutical Industry》来阐述，OHTA将不确定因子分为F1~F4。 (1) 不确定度因子F1：物种间差异 当使用人体研究来确定NOEL时，F1=1。同样，当临床前研究提示直接影响呼吸道时（如呼吸道刺激），F1=1。如果需要从动物推导到人类，需要考虑动物的代谢率与人类的差异。根据不同动物物种与人类之间的代谢率差异，选择不同的调整因子。例如，从小鼠推导到人类时，F1=7；从大鼠推导到人类时，F1=4；从豚鼠推导到人类时，F1=4；从狗推导到人类时，F1=3；从兔子推导到人类时，F1=2；从猴子推导到人类时，F1=2。 (2) 不确定度因子F2：物种内变异 F2表示同种物种个体对某些物质的药理学或毒理学效应的敏感性差异。通常情况下，当使用临床前研究或小规模临床研究来确定NOEL时，个体间的变异可能不明显，此时可以使用默认值10。然而，当发现对某种物质的生物反应存在显著变异时，无论是基于药代动力学的变异还是其他影响敏感性的因素，可以选择3到10之间的数值作为F2。 (3) 不确定度因子F3：毒理信息的充分性和质量 F3表示对人体健康结果的危害评估过程的可预测性的信心程度，该因子的大小应基于获取NOEL的信息的质量和完整性，而不考虑其他可用信息。 F3=1：当基于重复给药的广泛临床数据得出明确的NOEL时，使用该值。当从质量良好的临床前毒性研究或其他研究中获得明确的NOEL时，也使用该因子。 F3=3：当使用不涉及重复给药或质量不足以对职业场景进行明确推断的临床数据时，建议使用该值。当从亚慢性暴露的临床前研究中获得明确的NOEL时，也使用该因子。 F3=5-10：当使用药代动力学或药效学信息来更准确地推导动物数据与人类之间的关系时，应考虑使用此因子。 F3=3-10：当主要效应的数据表明存在最低观察效应水平（LOEL），而不是明确的NOEL，也应考虑使用该范围内的数值。 F3>>10：仅在存在对关键终点的研究进行解释时存在重大关切的特殊情况下，才会使用大于10的值。 当某种物质的可用信息与上述方案不完全匹配时，应根据上述指南的方案判断并分配适当的F3值。应充分记录F3分配的理由，并将其包括在OEL标准文件中。 (4) 不确定度因子F4：效应的性质和严重程度 前述的不确定度因子（F1-F3）通常涵盖了大多数研究结果的关键解释要素。然而，由于对健康产生不可逆或其他严重后果的某些靶器官或其他效应可能引起关注。不确定度因子F4在建立OEL的关键研究中提供了一定程度的保守性。 通常情况下，F4适用于被认为或证明具有剂量阈值的严重效应（例如非基因毒性引起的发育终点的不良效应和肿瘤）。在没有相关研究数据的情况下，可以使用F4来增加OEL的保守性。所使用的F4（Nature and Severity of Effect）的值取决于关注程度。例如，如果关注的是特定药物类别引起已知的胎儿畸形效应，且没有母体毒性的迹象，可以考虑使用F4=10。类似地，如果仅在伴随母体毒性时观察到胎儿效应，可以将较小的因子（例如F4=5）应用于同一终点。 综上所述，根据药物的OEL计算方法，通过考虑不确定度因子F1~F4，可以确定初步的OEL，待毒理学信息更新和补充，可以适当调整OEL。这些因子涵盖了物种间和物种内的差异、毒理信息充分性和质量以及效应的性质和严重程度，以确保工人在职业环境中受到适当的保护。制订OEL需要丰富的毒理学知识，建议由经验丰富的毒理学家进行。对于NOEL、NOAEL，甚至是OEL\OEB\PDE等信息，有现成权威资料建议直接引用。 OEB分级 一般根据OEL值、治疗剂量、LD50、NOAEL、致敏、致细胞突变、致癌、生殖毒性等综合确定。一般分为5级，当然有些药厂也有分为6级甚至7级的。OEB4级的产品线，应优先采用全程密闭化设备设施，设计密闭化工艺生产路径。OEB5级的产品线，应采用全程密闭化设备设施。涉及职业接触应选用隔离器、手套箱密闭操作、α-β阀、袋进袋出等控制措施。生产设备应选用自身高密闭性的，如三合一干燥器。OEB3级以下的危害相对小，不作赘述。 检测评估 检测一般有两个目的，一个是评估工人暴露，一个是测试制药设备采取的工程措施是否有效，检测布点可以按照ISPE（国际制药工程协会）的相关指南开展。 在制药设备采取的工程控制措施投入运行前，必须进行验证，常用乳糖甘露醇、萘普生钠、核黄素等替代物进行模拟操作，以每个OEB 的下限值作为防护性能目标值（CPT），按照ISPE要求进行区域和个体采样检测，对采样的结果进行统计学分析和评估，与所涉及的药物粉尘的OEL 进行风险评估，以保证工程控制措施的有效。根据评估结果制定周期监测计划。针对原料药的检测，目前国内基本没实验室可以开展，一般选择将样品快递到国外实验室分析。 由于外资药企审计等原因，目前国内制药企业也越来越重视API的OEL及OEB制订，OEL及OEB的制订技术含量还是挺高的，一般都是需要经验丰富的毒理学、职业卫生专家来制订。 参考资料 ISPE医药产品基于风险的生产（Risk-MaPP） ISPE制药设备药物粉尘控制性能评估 PSCI相关资料 强生公司OEL制订课件 辉瑞公司OEB分级课件 END 点分享 点收藏 点在看 点点赞