Ketoconazole

Brekiya® becomes the first and only DHE autoinjector that allows patients to self-administer the same medication used in hospitals in a ready-to-use form Product will be available for appropriate patients in the second half of 2025 BRIDGEWATER, N.J., May 15, 2025 (GLOBE NEWSWIRE) -- Amneal Pharmaceuticals, Inc. (Nasdaq: AMRX) (“Amneal” or the “Company”) today announced that the U.S. Food and Drug Administration (FDA) has approved Brekiya® (dihydroergotamine mesylate) injection, the first and only dihydroergotamine (DHE) autoinjector for the acute treatment of migraine with or without aura and the acute treatment of cluster headaches in adults.1,2 Brekiya autoinjector provides patients with the potential for sustained* pain relief† in a convenient, self-administered form.1,3,4 It contains the same medication (DHE) used in hospitals, now in a ready-to-use device.1,5 Brekiya autoinjector does not require refrigeration, assembly, or priming of the device.1 Patients can deliver one dose subcutaneously into the middle of the thigh.1 This may be beneficial for patients who respond inadequately to oral therapies due to lack of efficacy, experience nausea or vomiting during attacks, have gastroparesis, or delay dosing until too late into the attack.1,5,6 “We are thrilled to offer the first and only ready-to-use autoinjector for patients suffering from acute migraine and cluster headaches. Physicians are familiar with DHE, which is an effective and well-established therapy that provides sustained relief for headaches. Our single-dose autoinjector represents an innovative therapeutic option for patients that allows for quick self-administration of the medication during these painful attacks without visiting the emergency room,” said Joe Renda, Senior Vice President, Chief Commercial Officer – Specialty. DHE is commonly administered in emergency rooms, urgent care facilities, and headache clinics intravenously. DHE can be used at any point during a migraine attack, and may protect patients from headache recurrence.1,3,4 Approximately 39 million Americans are living with migraine7, and up to one million with cluster headache.8 Also, headache is the fourth most common reason for emergency department visits, and accounts for 3% of all emergency room visits in the United States.9 There are limited treatment options available for cluster headache, and Brekiya autoinjector represents a new treatment option for this underserved population.2 Do not take Brekiya autoinjector with strong CYP3A4 inhibitors including protease inhibitors and macrolide antibiotics. See additional Important Safety Information below. IndicationBrekiya autoinjector is a prescription medicine used for the acute treatment of migraine with or without aura and acute cluster headaches in adults. Brekiya autoinjector 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 autoinjector is safe and effective in children. IMPORTANT SAFETY INFORMATIONSerious or potentially life-threatening reductions in blood flow to the brain or extremities due to interactions between dihydroergotamine (the active ingredient in Brekiya autoinjector) 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 autoinjector 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 autoinjector.have taken any of the following medicines in the last 24 hours: sumatriptan, frovatriptan, ergotamine or ergotamine-type medicines, almotriptan, naratriptan, zolmitriptan, eletriptan, or rizatriptanhave taken any medicines that constrict your blood vessels or raise your blood pressure. Before you take Brekiya autoinjector, 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 autoinjector may cause preterm labor. Brekiya autoinjector 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 autoinjector may reduce breast milk supply and pass into your breast milk. Brekiya autoinjector may be harmful to your baby. Do not breastfeed your baby while taking Brekiya autoinjector and for 3 days after you use Brekiya autoinjector. Talk with your healthcare provider about the best way to feed your baby if you take Brekiya autoinjector. 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 autoinjector works. Your healthcare provider can tell you if it is safe to take Brekiya autoinjector 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 autoinjector is for injection under the skin (subcutaneous) only.Use Brekiya autoinjector 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. What are the possible side effects of Brekiya autoinjector?Brekiya autoinjector can cause serious side effects, including: Heart attack and other heart problems. Heart problems may lead to death. Stop taking Brekiya autoinjector 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 autoinjector 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.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 autoinjector may make their headaches worse. If your headaches get worse, your healthcare provider may decide to stop your treatment with Brekiya autoinjector.Preterm labor.Tissue changes (fibrotic complications). Inflammation and fiber-like tissue that is not normal (fibrosis) can occur around the lungs and stomach. 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 autoinjector. Call your healthcare provider for medical advice about side effects. How should I store Brekiya autoinjector? Store at room temperature between 68°F to 77°F (20°C to 25°C). Do not refrigerate or freeze.Protect Brekiya autoinjector from light.Keep Brekiya autoinjector 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. *Sustained represents a duration of approximately 24-72 hours2,3†Cluster headache results reported using IV administration.4 References: Brekiya [package insert]. Bridgewater, NJ: Amneal Pharmaceuticals LLC; 2025.Data on File. Amneal Pharmaceuticals LLC.Winner P, Ricalde O, Le Force B, Saper J, Margul B. Arch Neurol. 1996;53(2):180-184.Mather PJ, Silberstein SD, Schulman EA, Hopkins MM. Headache. 1991;31(8):525-532.Silberstein SD, Shrewsbury SB, Hoekman J. Headache. 2020;60(1):40-57. doi:10.1111/head.13700Aurora SK, Papapetropoulos S, Kori SH, Kedar A, Abell TL. Cephalalgia. 2013;33(6):408-415.https://migraineresearchfoundation.org/about-migraine/migraine-facts/https://americanmigrainefoundation.org/resource-library/cluster-headache-2/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. 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 Contact Anthony DiMeoVP, Investor Relations anthony.dimeo@amneal.comMedia ContactBrandon SkopSr. Director, Corporate CommunicationsBrandon.skop@amneal.com PP-PRS-DHE-US-0001 05/2025

5月7日，云顶新耀的布地奈德肠溶胶囊（耐赋康®）正式获得中国国家药品监督管理局（NMPA）的完全批准，这标志着该药物从附条件批准转为全面获批，也意味着其在IgA肾病治疗领域的地位进一步巩固，它成为国内首个且唯一获得完全批准的IgA肾病对因治疗药物，同时取消了对蛋白尿水平的限制，扩大了适用患者群体。布地奈德肠溶胶囊的完全批准基于全球III期临床试验NefIgArd研究的完整数据。这项研究覆盖了接受RAS抑制剂优化治疗的原发性IgA肾病患者，采用随机、双盲、多中心设计，结果显示，与安慰剂相比，布地奈德肠溶胶囊在9个月治疗期和15个月停药随访期内显著降低了蛋白尿水平，并减少了镜下血尿风险。更重要的是，它在估算肾小球滤过率（eGFR）这一关键指标上展现出统计学差异（p<0.0001），全球数据显示其减少肾功能衰退达50%，而中国亚组数据更为亮眼，延缓肾功能衰退达66%，预计将疾病进展至透析或肾移植的时间推迟12.8年。此前，布地奈德肠溶胶囊于2023年11月通过优先审评程序获得附条件批准，但当时适应症限于蛋白尿水平较高的患者，如尿蛋白肌酐比≥1.5g/g。此次取消限制后，所有具有疾病进展风险的IgA肾病患者均可使用，覆盖人群大幅扩大。例如，原本尿蛋白未达标的患者也能尽早接受对因治疗，从而延缓肾功能恶化。这一变化直接回应了临床需求，中国约有500万IgA肾病患者，每年新增超10万例，且东亚人群疾病进展更快、预后更差，传统治疗手段如激素和免疫抑制剂副作用大，疗效有限。IgA肾病的核心病理机制是半乳糖缺陷的IgA1抗体（Gd-IgA1）在肾脏沉积引发炎症反应，而这一抗体的产生与回肠末端的派尔集合淋巴结中的B细胞活化密切相关。布地奈德肠溶胶囊通过特殊的肠溶缓释工艺，将布地奈德靶向释放至回肠末端，抑制局部B细胞的活化和Gd-IgA1的生成，从而减少循环中的致病性免疫复合物，从上游阻断疾病进展。这种局部作用的设计大幅降低了全身副作用，布地奈德的首过代谢率高达90%，全身暴露量仅为10%，避免了传统激素的骨质疏松、高血糖等问题。价格曾是布地奈德肠溶胶囊推广的一大障碍。未纳入医保前，其疗程费用高达15万-18万元，9个月需服用约4盒，每盒1.5万-2万元，对普通患者而言负担沉重。但2024年11月，该药成功进入国家医保目录（乙类），并于2025年1月1日正式执行医保价格。截至今年3月底，全国26个省市已实现医保落地，覆盖医院和药店的渠道逐步完善。这一举措显著提升了药物可及性，尤其考虑到IgA肾病需长期管理，医保支持对患者坚持治疗至关重要。在实际应用中，布地奈德肠溶胶囊的用药方案为每日一次16mg（4粒），需整粒吞服且早餐前1小时空腹服用，以确保药物在肠道靶向释放。疗程固定为9个月，随后进入停药观察期，其疗效呈现延迟效应，蛋白尿最大降幅出现在停药后3个月（即第12个月），而肾功能保护作用在24个月的随访中持续显现。这提示医生和患者需耐心等待疗效显现，避免过早中断治疗。此外，药物代谢依赖CYP3A4酶，因此需避免与强效抑制剂，如酮康唑、西柚汁联用，以防血药浓度异常升高。对云顶新耀而言，布地奈德肠溶胶囊的完全批准是其商业化进程的关键一步。公司早在2019年通过授权引进获得该药在大中华区及新加坡的开发权益，2022年进一步扩展至韩国。目前，药物已在中国大陆、香港、澳门和新加坡上市，韩国及台湾地区预计年内跟进。为加速市场渗透，云顶新耀组建了200人的销售团队，目标覆盖全国600家医院，并与博鳌乐城先行区合作探索早期准入模式。财务方面，公司预计2025年实现现金流打平，天风证券预测其2025年营收或超18亿元。这一布局不仅依赖布地奈德肠溶胶囊，还需另一获批产品依拉环素（抗感染药）的协同效应，但IgA肾病领域的巨大需求仍是核心驱动力。布地奈德肠溶胶囊的临床价值已获国际权威指南认可。2024版KDIGO（改善全球肾脏病预后组织）指南将其列为推荐疗法，强调其作为“唯一可降低致病性IgA水平”的对因治疗地位。与传统治疗方案相比，其优势在于疗效持久且安全性更优，III期研究显示，即使停药后，eGFR下降速度仍较安慰剂组减少2.47mL/min/年，提示黏膜免疫调节的延续效应。尽管布地奈德肠溶胶囊疗效显著，但仍存在局限性。例如，其对严重肾功能不全（eGFR<30mL/min）患者无效，且价格即便纳入医保仍高于传统药物。未来，联合治疗可能是突破方向，与补体抑制剂联用，或与抗纤维化药物协同，有望进一步提升疗效。信息来源：[1]云顶新耀官媒[2]National Medical Products Administration (NMPA). (2024). Approval of Nefecon (Budesonide Delayed-Release Capsules) for IgA Nephropathy.[3]Everest Medicines. (2024). NefIgArd III Study Results Presented at ISN World Congress of Nephrology 2024.药事纵横投稿须知：稿费已上调，欢迎投稿