Zolmitriptan

Brekiya® autoinjector, a new specialty therapy from Amneal, is now available for prescription exclusively through Walgreens Specialty Pharmacy and Sterling Specialty Pharmacy BRIDGEWATER, N.J., Oct. 27, 2025 (GLOBE NEWSWIRE) -- Amneal Pharmaceuticals, Inc. (Nasdaq: AMRX) (“Amneal” or the “Company”) today announced the U.S. commercial launch of Brekiya® (dihydroergotamine mesylate) injection, the first and only ready-to-use dihydroergotamine (DHE) autoinjector approved for the acute treatment of migraine with or without aura and the acute treatment of cluster headaches in adults.1,2 The Brekiya autoinjector is now available by prescription exclusively through Walgreens Specialty Pharmacy and Sterling Specialty Pharmacy. “We are excited to introduce Brekiya autoinjector, making this innovative therapy broadly available to healthcare providers and patients. As the first and only self-administered, ready-to-use DHE autoinjector, Brekiya offers patients the ability to treat debilitating attacks in a convenient way and avoid visits to the emergency room. With our expanding neurology portfolio, Amneal is committed to supporting providers through comprehensive education and ensuring strong patient access as we bring Brekiya autoinjector to market,” said Joe Renda, Senior Vice President, Chief Commercial Officer – Specialty. Migraine affects approximately 43 million Americans3, and about 300,000 live with cluster headache.4 Headache disorders are also the fourth most common reason for U.S. emergency department visits, accounting nearly for 3% of cases.5 There are limited treatment options available for cluster headache, and Brekiya autoinjector represents a new treatment option for this underserved population.2 Information for Physicians and Patients: Brekiya is available only through prescription.Eligible commercially insured patients may pay as little as $40 per carton (4 single-dose autoinjectors per carton), applied automatically through the specialty pharmacy.To support healthcare providers, field reimbursement specialists will be available to assist with patient access, coverage and reimbursement questions. Do not take Brekiya with strong CYP3A4 inhibitors including protease inhibitors and macrolide antibiotics. See additional Important Safety Information below. IndicationBrekiya is a prescription medicine used for the acute treatment of migraine with or without aura and acute cluster headaches in adults. Brekiya is not used to prevent migraine or used to treat other types of headaches such as hemiplegic migraines (that make you unable to move on one side of your body) or basilar migraines (rare form of migraine with aura). It is not known if Brekiya is safe and effective in children. IMPORTANT SAFETY INFORMATIONBOXED WARNING: WARNING: PERIPHERAL ISCHEMIA FOLLOWING COADMINISTRATION WITH STRONG CYP3A4 INHIBITORSSerious or potentially life-threatening reductions in blood flow to the brain or extremities due to interactions between dihydroergotamine (the active ingredient in Brekiya) with strong CYP3A4 inhibitors (such as protease inhibitors and macrolide antibiotics) have been reported rarely. As a result, these medications should not be taken together. Do not use Brekiya if you: are taking medicines known as strong CYP3A4 inhibitors, such as: ritonavir, nelfinavir, indinavir, erythromycin, clarithromycin, ketoconazole, or itraconazole.have heart problems or a history of heart problems, or uncontrolled high blood pressure.have narrowing of blood vessels in your legs, arms, stomach, or kidneys (peripheral vascular disease).have sepsis, had vascular surgery, severe liver or kidney problems.are allergic to dihydroergotamine, ergot alkaloids, latex, or any of the ingredients in Brekiya.have taken any of the following medicines in the last 24 hours, before intended administration: sumatriptan, frovatriptan, ergotamine or ergotamine-type medicines, almotriptan, naratriptan, zolmitriptan, eletriptan, or rizatriptan.have taken any medicines that constrict your blood vessels or raise your blood pressure. Before you take Brekiya, tell your healthcare provider about all your medical conditions, including if you: have high blood pressure, liver problems, or kidney problems.have risk factors for heart disease, such as: high blood pressure, high cholesterol levels, smoke, are overweight, diabetes, family history of heart disease.are pregnant or plan to become pregnant. Brekiya may cause preterm labor. Brekiya should be avoided during pregnancy. Talk to your healthcare provider right away if you are pregnant or want to become pregnant.are breastfeeding or plan to breastfeed. Brekiya may reduce breast milk supply and pass into your breast milk. Brekiya may be harmful to your baby. Do not breastfeed your baby while taking Brekiya and for 3 days after you use Brekiya. Talk with your healthcare provider about the best way to feed your baby if you take Brekiya. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Especially tell your healthcare provider if you take: sumatriptan, ergot-type medicine, saquinavir, nefazodone, fluconazole, grapefruit juice, zileuton, nicotine, propranolol or other medicines that can lower your heart rate, any medicines that can increase your blood pressure, selective serotonin reuptake inhibitors. These are not all of the medicines that could affect how Brekiya works. Your healthcare provider can tell you if it is safe to take Brekiya with other medicines. How should I use Brekiya autoinjector? Certain people should take their first dose of Brekiya autoinjector in their healthcare provider’s office or in another medical setting.Brekiya is for injection under the skin (subcutaneous) only.Use Brekiya exactly as your healthcare provider tells you to use it.Each autoinjector contains one dose (1 mg).If your headache comes back after the first complete dose, you may give yourself up to 2 more doses as needed. Wait at least one hour between doses.Do not inject more than 3 doses (3 mg) of Brekiya autoinjector in a 24-hour period or 6 doses (6 mg) in a 1-week (7 day) period.Using BREKIYA for 10 or more days in 1 month may make your headache worse. What are the possible side effects of Brekiya?Brekiya can cause serious side effects, including: Heart attack and other heart problems. Heart problems may lead to death. Stop taking Brekiya and get emergency medical help right away if you have any symptoms of a heart attack, such as: numbness or tingling in your fingers and toes, muscle pain or cramps in your arms and legs, weakness in your legs, temporary speeding or slowing of your heart rate, or swelling or itching. Brekiya is not for people with risk factors for heart disease unless a heart exam is done and shows no problem.Stroke. Stop using Brekiya autoinjector and get emergency medical help right away if you have any of the symptoms of a stroke, such as face drooping, slurred speech and unusual weakness.Changes in color or sensation in your fingers and toes (Raynaud’s syndrome).Stomach and intestinal problems.Increased blood pressure.Medicine overuse headache. Some people who use too much Brekiya may make their headaches worse. If your headaches get worse, your healthcare provider may decide to stop your treatment with Brekiya.Preterm labor.Tissue changes (fibrotic complications). Inflammation and fiber-like tissue that is not normal (fibrosis) can occur around the lungs and stomach.The most common but serious side effects of Brekiya are heart problems that happen but may lead to death. These heart problems include: temporary squeezing of arteries that supply the heart (coronary artery vasospasm)temporary decrease of blood flow to the heart (transient myocardial ischemia)heart rhythm problems (ventricular tachycardia and ventricular fibrillation). Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all of the possible side effects of Brekiya. Call your healthcare provider for medical advice about side effects. How should I store Brekiya? Store at room temperature between 68°F to 77°F (20°C to 25°C). Do not refrigerate or freeze.Protect Brekiya from light.Keep Brekiya in the original pack until ready to use. To report SUSPECTED ADVERSE REACTIONS, contact Amneal Specialty, a division of Amneal Pharmaceuticals LLC at 1-877-835-5472, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. Please see full Prescribing Information, including Boxed Warning, Medication Guide, and Instructions for Use at Brekiya.com. References: Brekiya package insert. Bridgewater, NJ: Amneal Pharmaceuticals LLC; 2025.Data on File. Amneal Pharmaceuticals LLC.Cohen F, et al. Headache. 2024;64(5):516-532.Fischera M et al. Cephalalgia. 2008;28(6)614-618.Phelan, M, Thompson NR, Zubair A et al. Emergency department utilization among patients who receive outpatient specialty care for headache: A retrospective cohort study analysis. Headache. 2023;63:472–483. Note: Brekiya is a registered trademark of Amneal Pharmaceuticals LLC. About AmnealAmneal Pharmaceuticals, Inc. (Nasdaq: AMRX), headquartered in Bridgewater, NJ, is a global biopharmaceutical company. We make healthy possible through the development, manufacturing, and distribution of a diverse portfolio of over 280 pharmaceuticals, primarily within the United States. In its Affordable Medicines segment, the Company is expanding across a broad range of complex product categories and therapeutic areas, including injectables and biosimilars. In its Specialty segment, Amneal has a growing portfolio of branded pharmaceuticals focused primarily on central nervous system and endocrine disorders. Through its AvKARE segment, the Company is a distributor of pharmaceuticals and other products for the U.S. federal government, retail, and institutional markets. For more information, please visit www.amneal.com and follow us on LinkedIn. Cautionary Statement on Forward-Looking StatementsCertain statements contained herein, regarding matters that are not historical facts, may be forward-looking statements (as defined in the U.S. Private Securities Litigation Reform Act of 1995). Such forward-looking statements include statements regarding management’s intentions, plans, beliefs, expectations, financial results, or forecasts for the future, including among other things: discussions of future operations; expected or estimated operating results and financial performance; and statements regarding our positioning, including our ability to drive sustainable long-term growth, and other non-historical statements. Words such as “plans,” “expects,” “will,” “anticipates,” “estimates,” and similar words, or the negatives thereof, are intended to identify estimates and forward-looking statements. The forward-looking statements contained herein are also subject generally to other risks and uncertainties that are described from time to time in the Company’s filings with the Securities and Exchange Commission, including under Item 1A, “Risk Factors” in the Company’s most recent Annual Report on Form 10-K and in its subsequent reports on Forms 10-Q and 8-K. Forward-looking statements included herein speak only as of the date hereof and we undertake no obligation to revise or update such statements to reflect the occurrence of events or circumstances after the date hereof. Investor ContactAnthony DiMeoVP, Investor Relationsanthony.dimeo@amneal.comMedia ContactBrandon SkopSr. Director, Corporate Communicationsbrandon.skop@amneal.com

前文链接：当前质谱在药物分析中的作用（上） 2.2.4 生物制药PTM分析技术新突破 在生物制药表征领域，反相液相色谱(RPLC)和HILIC作为两大主流技术，为翻译后修饰(PTM)分析提供了互补视角。RPLC擅长解析疏水性变体和结构完整性，而HILIC则在聚糖分析中展现出独特优势。当这些技术与质谱联用时，能够获得精确质量数以识别复杂修饰。 然而，大分子蛋白质的LC-MS分析面临诸多挑战：分子尺寸效应导致传质受限，构象异质性影响分离效率，而传统三氟乙酸(TFA)添加剂虽然提升色谱性能，却会显著抑制电喷雾电离(ESI)效率。这种抑制源于TFA与蛋白质形成的稳定离子对复合物，以及其对喷雾稳定性的负面影响。更棘手的是，高温条件虽然能改善分离，却可能加速蛋白质降解并缩短色谱柱寿命。 面对这些挑战，行业正在探索更温和的分析条件，在保持足够分离效率的同时，最大限度地提升质谱灵敏度。这一平衡对于实现生物制药全面、准确的PTM表征至关重要，也为下一代分析方法开发指明了方向。 2.2.5 翻译后修饰的分析：替代方法 在生物制药翻译后修饰分析领域，研究人员正在探索突破性的替代方案来克服传统TFA方法的局限性。最新研究表明，采用0.03% TFA与0.07%甲酸(FA)的混合体系，配合60-65°C的温和条件，不仅保持了色谱分离效率，更使质谱灵敏度提升超过40%。这一优化方案特别适用于单抗亚基的分析，为生物制药表征提供了更优选择。 二氟乙酸(DFA)作为新兴的离子对试剂展现出独特优势：其酸性和疏水性较TFA更低，能有效改善电喷雾液滴表面张力，在特定情况下甚至展现出优于TFA的分离分辨率。虽然目前LC-MS级DFA的供应限制影响了其广泛应用，但它无疑代表了未来发展方向。与此同时，创新的正丁醇添加剂策略通过"屏蔽"硅醇基团，实现了无需高温的高效分离，这一方法在与聚苯固定相联用时，展现出从完整蛋白到肽段的多层次分析潜力。这些技术进步正在推动生物制药分析进入新纪元，在保持分离性能的同时显著提升检测灵敏度，为更精准的PTM表征开辟了道路。 2.2.6 疏水非均质性的测定 在生物制药质量控制中，疏水性变异分析正经历重要技术突破。传统疏水相互作用色谱(HIC)虽然能有效分析由构象变化、PTM或ADC药物载荷引起的疏水变异体，但其高盐流动相与质谱的兼容性问题长期困扰着研究人员。 最新开发的"补置和分裂流"平台巧妙解决了这一难题：通过柱后稀释降低盐浓度，再经分流调节流速，成功实现了HIC与天然纳米电喷雾电离的在线联用。这一创新已在单抗和ADC分析中获得验证，同时保持了优异的色谱分辨率和质谱数据质量。 更令人振奋的是，使用乙酸铵等挥发性盐的改良HIC方法，不仅实现了与天然质谱的在线偶联，还能同步完成高阶结构表征和关键质量属性评估。这些技术进步为生物制药的全面质量控制提供了全新工具，将显著提升产品表征的深度和效率。 2.3 蛋白质药物在肽水平上的分析 肽水平的分析方法涵盖了与蛋白质水平相比更小尺寸分子的分析。这些方法不会像较大的完整单克隆抗体或其亚基那样受到大小和电离不足的高度挑战。尽管如此，将PTM作为CQA进行分析在生物制药表征中仍然是一个巨大的挑战（Walsh，2010）。使用肽图分析方法研究了ICH Q6B（人用药品注册技术要求协调国际会议，1999a）要求的结构特征，包括蛋白质一级结构和现有PTM。获得的结果在开发决策中起着至关重要的作用。应监测 PTM 的光谱，特别是氧化、脱酰胺、糖基化、环化、削波、扰乱等。 2.3.1 肽图分析工作流程 肽图分析作为生物制药研发的关键技术，通过特异性蛋白酶（如胰蛋白酶、Lys-C等）的精准酶切，结合LC-UV和LC-HRMS的协同分析，实现了从主要肽序列确认到PTM精确定位的全面表征。这项技术不仅能检测PTM导致的保留行为变化，更能通过高分辨质谱提供精确的序列信息和修饰定位，特别是对糖基化位点的占有率和异质性评估具有独特优势。 然而，传统肽图分析方法面临着样品制备复杂、耗时且易产生伪影（如脱酰胺、氨甲酰化等）的挑战。为提升分析效率，行业正在探索创新方法，包括微波辅助和高压消化等加速技术。虽然RPLC-UV仍是QC实验室的常规选择，但质谱技术的引入显著提升了方法的选择性和可靠性。一项为期一年的mAb结构变异研究证实，经过充分验证的RPLC-MS方法展现出优异的精密度和稳健性，能够有效监控生产工艺变化并支持临床试验批次的质量评估。这些技术进步正在推动肽图分析从研发工具向常规质量控制手段的转变。 2.4 聚糖谱分析 在生物制药领域，聚糖谱分析正成为确保产品质量的核心技术。糖基化修饰不仅影响治疗性蛋白的生物活性和理化性质，更直接决定了产品的疗效和安全性。研究表明，单抗和Fc融合蛋白中特定的糖型结构——如末端唾液酸化能显著延长半衰期，而半乳糖残基则可能加速清除——这使得糖基化成为不可或缺的关键质量属性。 面对糖型结构的复杂性，现代分析技术提供了多维度解决方案。HILIC-MS凭借其高灵敏度成为糖型分析的有力工具，而CE技术则以其高效分离能力在GMP环境中大显身手。特别值得关注的是CE-FTMS等高分辨技术，能够精确解析不同唾液酸化程度的糖型结构，为生物类似药开发提供关键数据支持。这些技术进步正在推动聚糖分析从研发向生产质控的转化，为每一支生物制药产品的质量保驾护航。 03 未来趋势 在药物分析领域，我们正见证着一场技术革命。小分子LC-MS分析正朝着简化样品制备、自动化工作流程和缩短分析时间的方向快速发展。环境电离质谱技术（如DESI和DART）的出现，实现了近乎实时的样品分析，而单四极杆质谱仪则为常规QC提供了经济高效的解决方案。 生物制药分析正迎来多维技术的时代。通过结合不同色谱模式（IEX、HIC、SEC等）的多维方法，研究人员能够获得更全面的产品信息。离子淌度谱（IMS）技术的引入，为蛋白质高阶结构分析提供了新的视角，而在线样品制备系统则显著提升了分析效率和一致性。 自动化正成为行业标配，从样品制备到数据分析的全流程自动化不仅提高了效率，更确保了结果的准确性和可重复性。特别是4D-LC-MS等创新技术，实现了从完整蛋白到肽段的多层次分析，为质量控制提供了前所未有的深度。 未来，人工智能和机器学习将进一步提升数据处理能力，帮助我们从复杂的质谱数据中提取更有价值的信息。这些技术进步正在重塑药物分析的格局，为开发更安全、更有效的治疗药物铺平道路。 编者注 以上总结仅代表个人对文献的理解，仅供研究参考使用，不用于商业用途。若上述理解内容有误，请以文献原文为主。 参考文献 [1]Khalikova M, Jireš J, Horáček O, Douša M, Kučera R, Nováková L. What is the role of current mass spectrometry in pharmaceutical analysis?[J]. Mass Spectrometry Reviews, 2024, 43(3): 560-609. [2]Patha R V P, Dasa K, Bhoomireddy R D, Panchakarla R K, Mullangi S. Development and validation of a highly sensitive LC-MS/MS method for the quantification of N-nitroso-desmethyl-zolmitriptan: a nitrosamine impurity in zolmitriptan[J]. Separation Science Plus, 2025, 8(9).