OPSYNVI® combines two proven treatments with established efficacy and safety profiles into one tablet to be taken once daily, offering an option that helps to support the implementation of clinical guideline recommendations for early use of combination therapy.1

OPSYNVI®将两种经过验证的治疗方法与既定的疗效和安全性组合成一片，每天服用一次，提供了一种选择，有助于支持早期使用联合治疗的临床指南建议的实施。

The comprehensive PAH portfolio at Johnson & Johnson now includes treatments that address all three foundational and guideline-recommended pathways for this rare, progressive disease.2

强生公司的综合PAH组合现在包括针对这种罕见的进行性疾病的所有三种基础和指南推荐途径的治疗方法。

Approval is based on the results from the pivotal Phase 3 A DUE study, which met its co-primary endpoints, demonstrating significant pulmonary hemodynamic improvement.1

批准是基于关键的第3阶段A DUE研究的结果，该研究符合其共同主要终点，表明肺血流动力学显着改善。

RARITAN, N.J., March 22, 2024  /PRNewswire/ -- Johnson & Johnson today announced that the U.S. Food and Drug Administration (FDA) has approved OPSYNVI® – a single-tablet combination of macitentan, an endothelin receptor antagonist (ERA), and tadalafil, a phosphodiesterase 5 (PDE5) inhibitor – for the chronic treatment of adults with pulmonary arterial hypertension (PAH, World Health Organization [WHO] Group I) and WHO functional class (FC) II-III.1 OPSYNVI® may be used in patients with PAH who are treatment-naïve or who are already on an ERA, PDE5 inhibitor or both.

新泽西州拉瑞坦（RARITAN），2024年3月22日/PRNewswire/--强生公司今天宣布，美国食品和药物管理局（FDA）已批准OPSYNVI®-内皮素受体拮抗剂（ERA）马西替坦和磷酸二酯酶5（PDE5）抑制剂他达拉非的单一片剂组合-用于慢性治疗成人肺动脉高压（PAH，世界卫生组织（WHO）第一组）和WHO功能类别（FC）II-III.1 OPSYNVI®可用于未接受治疗或已接受ERA，PDE5抑制剂或两者都有。

OPSYNVI® may be used in patients who are currently treated concomitantly with stable doses of macitentan 10 mg and tadalafil 40 mg (20 mg x 2) as separate tablets.1.

OPSYNVI®可用于目前同时服用稳定剂量的马西替坦10 mg和他达拉非40 mg（20 mg x 2）作为单独片剂的患者。

PAH is a rare, progressive and life-threatening blood vessel disorder characterized by the constriction of small pulmonary arteries and elevated blood pressure in the pulmonary circulation that eventually leads to right heart failure.2 An estimated 500 to 1,000 new cases of PAH are diagnosed each year in the U.S., classifying the disease as a rare condition.3.

PAH是一种罕见的，进行性和危及生命的血管疾病，其特征是小肺动脉收缩和肺循环中的血压升高，最终导致右心衰竭[2]。美国每年估计有500至1000例新发PAH病例，将该疾病归类为罕见病。

The 2022 European Society of Cardiology (ESC) / European Respiratory Society (ERS) clinical guidelines recommend initial combination therapy of an ERA and a PDE5 inhibitor for patients with idiopathic PAH, heritable drug-associated PAH, or PAH-associated with connective tissue disease without cardiopulmonary comorbidities at low or intermediate risk.2 .

2022年欧洲心脏病学会（ESC）/欧洲呼吸学会（ERS）临床指南建议对特发性PAH，遗传性药物相关PAH或与结缔组织病相关的PAH患者进行ERA和PDE5抑制剂的初始联合治疗，而无心肺合并症处于低风险或中等风险。

'Clinical guidelines recommend treating patients with initial and sequential dual-combination therapy, regardless of risk at initial diagnosis and follow-up. Historically, this required patients to take multiple pills because no single-tablet combination therapy targeting two or more pathways was available,' said Kelly Chin, M.D., Professor of Internal Medicine and Director of the Pulmonary Hypertension Program at UT Southwestern Medical Center, and an investigator in the A DUE study.* 'As administration of macitentan and tadalafil together are commonly prescribed for initial therapy for PAH, the introduction of a single tablet combining both is promising for clinicians treating patients as it may help bridge the gap between clinical guidelines and everyday clinical practice, while offering a patient-friendly approach to support initial combination therapy and rapid escalation for the appropriate patients.'.

“临床指南建议对患者进行初始和序贯双重联合治疗，无论初始诊断和随访的风险如何。“从历史上看，这需要患者服用多种药物，因为没有针对两种或两种以上途径的单一片剂联合治疗可用，”犹他州西南医学中心内科教授兼肺动脉高压项目主任凯利·钦（Kelly Chin）医学博士（Kelly Chin，M.D.）以及A DUE研究中的一名研究人员说。“由于马西替坦和他达拉非的联合给药通常用于PAH的初始治疗，因此将两者结合的单一片剂的引入对于临床医生治疗患者是有希望的，因为它可能有助于弥合临床指南与日常临床实践之间的差距，同时提供一种患者友好的方法来支持初始联合治疗并为适当的患者快速升级。”

The FDA's approval of OPSYNVI® is based on the results from the pivotal Phase 3 A DUE study, in which OPSYNVI® demonstrated greater reduction in Pulmonary Vascular Resistance (PVR) after 16 weeks versus tadalafil or macitentan monotherapy. OPSYNVI® has a Boxed Warning due to the risk of embryo-fetal toxicity and requires female patients to enroll in the Macitentan-Containing Products Risk Evaluation and Mitigation Strategy (REMS) program.1.

FDA对OPSYNVI®的批准是基于关键的第3阶段A期研究的结果，其中OPSYNVI®在16周后表现出比他达拉非或马西替坦单药治疗更大的肺血管阻力（PVR）降低。OPSYNVI®由于存在胚胎-胎儿毒性风险而发出盒装警告，并要求女性患者参加含马西替坦的产品风险评估和缓解策略（REMS）计划。

With the approval, Johnson & Johnson now offers a PAH portfolio addressing all three foundational and guideline-recommended pathways – nitric oxide, endothelin, and prostacyclin.

经批准，强生公司现在提供了一个PAH组合，解决了所有三个基础和指南推荐的途径-一氧化氮，内皮素和前列环素。

'People with PAH often live with the burden of taking many pills each day, which can pose challenges,' said James F. List, M.D., Ph.D., Global Therapeutic Area Head, whose team oversees a portfolio of programs including Pulmonary Hypertension at Johnson & Johnson. 'We're thrilled to bring this single-tablet combination therapy to patients, as it has the potential to optimize disease management and fulfill a significant unmet need in supporting recently updated treatment guidelines that call for initial or early combination treatment.'.

全球治疗领域负责人、医学博士詹姆斯·李斯特（JamesF.List）说，多环芳烃（PAH）患者经常每天服用大量药物，这可能会带来挑战。李斯特的团队负责监督强生（Johnson&Johnson）的肺动脉高压等一系列项目我们很高兴将这种单片剂联合疗法带给患者，因为它有可能优化疾病管理，并满足最近更新的治疗指南（要求初始或早期联合治疗）的重大未满足需求。

About OPSYNVI®1OPSYNVI® is a combination of macitentan, an endothelin receptor antagonist (ERA), and tadalafil, a phosphodiesterase 5 (PDE5) inhibitor indicated for the chronic treatment of pulmonary arterial hypertension (PAH, WHO Group I) in adult patients of WHO functional class (FC) II-III.

关于OPSYNVI®1OPSYNVI®是内皮素受体拮抗剂（ERA）马西替坦和磷酸二酯酶5（PDE5）抑制剂他达拉非的组合，用于慢性治疗WHO功能II-III级成年患者的肺动脉高压（PAH，WHO I组）。

Individually, macitentan reduces the risk of clinical worsening events and hospitalization, and tadalafil improves exercise ability.

单独而言，马西替坦可降低临床恶化事件和住院的风险，他达拉非可改善运动能力。

About the A DUE Study1,4The A DUE study was a double-blind, randomized, active-controlled, multi-center, adaptive, parallel-group study designed to compare the efficacy and safety of OPSYNVI® to macitentan and tadalafil monotherapies in adult patients with PAH (WHO FC II or III). The three-arm trial enrolled patients from across 76 sites in 16 countries/territories worldwide who were treatment-naïve or on a stable dose of an endothelin receptor antagonist (ERA), or a phosphodiesterase 5 (PDE5) inhibitor, for at least three months.

关于A DUE研究1,4 A DUE研究是一项双盲，随机，主动对照，多中心，适应性，平行组研究，旨在比较OPSYNVI®与马西替坦和他达拉非单药治疗成人PAH患者的疗效和安全性（WHO FC II或III）。这项三臂试验招募了来自全球16个国家/地区76个地点的患者，这些患者未接受治疗或服用稳定剂量的内皮素受体拮抗剂（ERA）或磷酸二酯酶5（PDE5）抑制剂至少三个月。

The primary endpoint was change from baseline in PVR at the end of double-blind treatment at 16 weeks and was considered met if macitentan and tadalafil fixed-dose combination (FDC) treatment was superior to both monotherapies. Following the treatment period, patients transitioned to the open-label treatment period for 24 months..

主要终点是在16周双盲治疗结束时PVR的基线变化，如果马西替坦和他达拉非固定剂量联合（FDC）治疗优于两种单一疗法，则认为符合。治疗期结束后，患者过渡到开放标签治疗期24个月。

OPSYNVI® is the combination of macitentan and tadalafil indicated for the chronic treatment of adults with pulmonary arterial hypertension (PAH, WHO Group I and WHO Functional Class [FC] II-III).

OPSYNVI®是马西替坦和他达拉非的组合，用于慢性治疗成人肺动脉高压（PAH，WHO I组和WHO功能II-III级）。

Individually, macitentan reduces the risk of clinical worsening events and hospitalization, and tadalafil improves exercise ability.

单独而言，马西替坦可降低临床恶化事件和住院的风险，他达拉非可改善运动能力。

IMPORTANT SAFETY INFORMATION

重要安全信息

WARNING: EMBRYO-FETAL TOXICITY

警告：胚胎-胎儿毒性

Do not administer OPSYNVI® to a pregnant female because it may cause fetal harm.

不要给孕妇服用OPSYNVI®，因为它可能会对胎儿造成伤害。

Females of reproductive potential: Exclude pregnancy before the start of treatment, monthly during treatment, and 1 month after stopping treatment. Prevent pregnancy during treatment and for one month after stopping treatment by using acceptable methods of contraception.

具有生殖潜力的女性：在治疗开始前，治疗期间每月和停止治疗后1个月不包括怀孕。使用可接受的避孕方法，在治疗期间和停止治疗后一个月内预防怀孕。

For all female patients, OPSYNVI® is available only through a restricted program called the Macitentan-Containing Products Risk Evaluation and Mitigation Strategy (REMS).

对于所有女性患者，OPSYNVI®只能通过一项名为含Macitentan的产品风险评估和缓解策略（REMS）的受限计划获得。

CONTRAINDICATIONS

禁忌症

Pregnancy: OPSYNVI® may cause fetal harm when administered to a pregnant woman and is contraindicated in females who are pregnant. If OPSYNVI® is used during pregnancy, advise the patient of the potential risk to a fetus.

怀孕：OPSYNVI®给孕妇服用时可能会对胎儿造成伤害，对怀孕女性禁用。如果在怀孕期间使用OPSYNVI®，请告知患者对胎儿的潜在风险。

Hypersensitivity: OPSYNVI® is contraindicated in patients with a history of a hypersensitivity reaction to macitentan, tadalafil, or any component of the product.

超敏反应：OPSYNVI®禁用于对马西替坦、他达拉非或产品任何成分有超敏反应史的患者。

Concomitant Organic Nitrates: OPSYNVI® is contraindicated in patients who are using any form of organic nitrate, either regularly or intermittently. Do not use nitrates within 48 hours of the last dose of OPSYNVI®.

伴随的有机硝酸盐：OPSYNVI®禁用于定期或间歇性使用任何形式有机硝酸盐的患者。在最后一剂OPSYNVI®后48小时内不要使用硝酸盐。

Concomitant Guanylate Cyclase (GC) Stimulators: OPSYNVI® is contraindicated in patients using GC stimulators such as riociguat.

伴随的鸟苷酸环化酶（GC）刺激剂：OPSYNVI®禁用于使用GC刺激剂（如riociguat）的患者。

WARNINGS AND PRECAUTIONS

警告和注意事项

Embryo-fetal Toxicity and Macitentan-Containing Products REMS:

胚胎-胎儿毒性和含马西替坦的产品REMS：

Due to the risk of embryo-fetal toxicity, OPSYNVI® is available for females only through a restricted program called the Macitentan-Containing Products REMS Program. For females of reproductive potential, exclude pregnancy prior to initiation of therapy, ensure use of acceptable contraceptive methods, and obtain monthly pregnancy tests. .

由于存在胚胎-胎儿毒性的风险，OPSYNVI®仅通过一种称为含马西替坦产品REMS计划的限制性程序可供女性使用。对于具有生殖潜力的女性，在开始治疗之前排除怀孕，确保使用可接受的避孕方法，并每月进行妊娠检查。

Notable requirements of the Macitentan-Containing Products REMS Program include:

含马西替坦产品REMS计划的显著要求包括：

Prescribers must be certified with the program by enrolling and completing training.

处方者必须通过注册和完成培训获得该计划的认证。

All females, regardless of reproductive potential, must enroll in the Macitentan-Containing Products REMS Program prior to initiating OPSYNVI®. Male patients are not enrolled in the REMS.

在启动OPSYNVI®之前，所有女性，无论其生殖潜力如何，都必须参加含马西替坦的产品REMS计划。男性患者未参加REMS。

Females of reproductive potential must comply with the pregnancy testing and contraception requirements.

具有生殖潜能的女性必须遵守妊娠测试和避孕要求。

Pharmacies must be certified with the program and must only dispense to patients who are authorized to receive OPSYNVI®.

药店必须获得该计划的认证，并且只能分配给授权接受OPSYNVI®的患者。

Hepatotoxicity

肝毒性

ERAs have caused elevations of aminotransferases, hepatotoxicity, and liver failure.

ERA导致氨基转移酶升高，肝毒性和肝衰竭。

In the double-blind arm of the A DUE study, the incidence of elevated aminotransferases >3 x ULN was 1.0%, and >8 x ULN was 1.0% for OPSYNVI®. In the combined double-blind/open-label arm, the incidence was 3.4% and 1.1%, respectively.

在A DUE研究的双盲组中，OPSYNVI®的转氨酶升高>3 x ULN的发生率为1.0%，而>8 x ULN的发生率为1.0%。在联合双盲/开放标签组中，发生率分别为3.4%和1.1%。

Discontinuations for hepatic adverse events in the double-blind and combined double-blind/open-label arms study for OPSYNVI® were 0.9% and 2.2%, respectively.

OPSYNVI®双盲和双盲/开放标签联合arms研究中肝脏不良事件的停药率分别为0.9%和2.2%。

Obtain liver enzyme tests prior to initiation of OPSYNVI® and repeat during treatment as clinically indicated.

在开始OPSYNVI®之前进行肝酶测试，并在临床指示的治疗过程中重复进行。

Advise patients to report symptoms suggesting hepatic injury (nausea, vomiting, right upper quadrant pain, fatigue, anorexia, jaundice, dark urine, fever, or itching). If clinically relevant aminotransferase elevations occur, or if elevations are accompanied by an increase in bilirubin >2 x ULN, or by clinical symptoms of hepatotoxicity, discontinue OPSYNVI®.

建议患者报告肝损伤的症状（恶心、呕吐、右上腹疼痛、疲劳、厌食、黄疸、尿黑、发烧或瘙痒）。如果发生临床相关的转氨酶升高，或者升高伴随着胆红素>2的增加 x ULN或肝毒性的临床症状，停止OPSYNVI®。

Consider re-initiation of OPSYNVI® when hepatic enzyme levels normalize in patients who have not experienced clinical symptoms of hepatotoxicity. .

在没有出现肝毒性临床症状的患者中，当肝酶水平正常化时，考虑重新启动OPSYNVI®。

Do not initiate OPSYNVI® in patients with elevated aminotransferases (> 3 x ULN) at baseline. Patients with severe hepatic cirrhosis (Child-Pugh Class C) have not been studied; therefore, avoid use of OPSYNVI®.

不要在基线时氨基转移酶升高（>3 x ULN）的患者中启动OPSYNVI®。尚未研究严重肝硬化患者（Child-Pugh C级）；因此，避免使用OPSYNVI®。

Hypotension

低血压

OPSYNVI® has vasodilatory properties that may result in transient decreases in blood pressure. Prior to prescribing OPSYNVI®, physicians should carefully consider whether patients with underlying cardiovascular disease could be adversely affected by such vasodilatory effects. Patients with pre-existing hypotension, autonomic dysfunction, or left ventricular outflow obstruction, may be particularly sensitive to the actions of vasodilators. .

OPSYNVI®具有血管舒张特性，可能导致血压短暂下降。在开具OPSYNVI®之前，医生应仔细考虑潜在心血管疾病患者是否会受到这种血管舒张作用的不利影响。先前存在低血压，自主神经功能障碍或左心室流出道梗阻的患者可能对血管扩张剂的作用特别敏感。

Hemoglobin Decrease

血红蛋白降低

Decreases in hemoglobin concentration and hematocrit have occurred following administration of other ERAs and were observed in clinical studies with OPSYNVI® and OPSUMIT®. These decreases occurred early and stabilized thereafter.

服用其他ERA后，血红蛋白浓度和血细胞比容降低，并且在OPSYNVI®和OPSUMIT®的临床研究中观察到。这些下降发生得很早，之后趋于稳定。

In the placebo-controlled study of OPSUMIT® in PAH, OPSUMIT® 10 mg caused a mean decrease in hemoglobin from baseline to up to 18 months of about 1.0 g/dL compared to no change in the placebo group. A decrease in hemoglobin to below 10.0 g/dL was reported in 8.7% of the OPSUMIT® 10 mg group and in 3.4% of the placebo group.

在OPSUMIT®在PAH中的安慰剂对照研究中，与安慰剂组相比，OPSUMIT®10 mg导致血红蛋白从基线平均下降至18个月，约为1.0 g/dL。据报道，OPSUMIT®10 mg组中有8.7%的血红蛋白降至10.0 g/dL以下，安慰剂组中有3.4%的血红蛋白降至10.0 g/dL以下。

Similar results were observed in the trial with OPSYNVI®..

在使用OPSYNVI®的试验中观察到了类似的结果。

Decreases in hemoglobin seldom require transfusion. Initiation of OPSYNVI® is not recommended in patients with severe anemia. Measure hemoglobin prior to initiation of treatment and repeat during treatment as clinically indicated.

血红蛋白减少很少需要输血。严重贫血患者不建议开始使用OPSYNVI®。在开始治疗之前测量血红蛋白，并根据临床指示在治疗期间重复。

Worsening Pulmonary Veno-Occlusive Disease (PVOD)

恶化的肺静脉闭塞性疾病（PVOD）

Since there are no clinical data on administration of OPSYNVI® tablets to patients with veno-occlusive disease, administration of OPSYNVI® tablets to such patients is not recommended. Should signs of pulmonary edema occur when OPSYNVI® tablets are administered, the possibility of associated PVOD should be considered.

由于没有关于静脉闭塞性疾病患者服用OPSYNVI®片剂的临床数据，因此不建议向此类患者服用OPSYNVI®片剂。如果服用OPSYNVI®片剂时出现肺水肿迹象，应考虑相关PVOD的可能性。

If confirmed, discontinue OPSYNVI®..

如果确认，停止OPSYNVI®。

Visual Loss and Hearing Impairment

视力丧失和听力障碍

Non–arteritic anterior ischemic optic neuropathy (NAION), a cause of decreased vision, including permanent loss of vision, has been reported postmarketing in temporal association with the use of phosphodiesterase type 5 (PDE5) inhibitors, including tadalafil. Most, but not all, of these patients had underlying anatomic or vascular risk factors for development of NAION. .

据报道，非动脉炎性前部缺血性视神经病变（NAION）是视力下降（包括永久性视力丧失）的原因，上市后与使用5型磷酸二酯酶（PDE5）抑制剂（包括他达拉非）有关。这些患者中的大多数（但不是全部）具有NAION发展的潜在解剖或血管危险因素。

Use of OPSYNVI® in patients with known hereditary degenerative retinal disorders, including retinitis pigmentosa, is not recommended.

不建议在患有已知遗传性退行性视网膜疾病（包括色素性视网膜炎）的患者中使用OPSYNVI®。

Cases of sudden decrease or loss of hearing, which may be accompanied by tinnitus and dizziness, have been reported in patients taking tadalafil.

据报道，服用他达拉非的患者听力突然下降或丧失，可能伴有耳鸣和头晕。

Fluid Retention

液体滞留

Peripheral edema and fluid retention are known clinical consequences of PAH and known effects of ERAs, and heart failure has been reported in patients taking OPSYNVI®. In the clinical study of OPSYNVI® in PAH, the incidence of peripheral edema/fluid retention was 20.6% in the active-controlled and 17.3% in the double-blind/open-label arm.

外周水肿和液体潴留是PAH的已知临床后果和ERAs的已知作用，服用OPSYNVI®的患者已报告心力衰竭。在OPSYNVI®治疗PAH的临床研究中，主动控制组外周水肿/液体潴留的发生率为20.6%，双盲/开放标签组为17.3%。

Patients with underlying left ventricular dysfunction may be at particular risk for developing significant fluid retention after initiation of ERA treatment.

在开始ERA治疗后，患有潜在左心室功能障碍的患者可能特别容易出现明显的液体潴留。

Monitor for signs of fluid retention after OPSYNVI® initiation. If clinically significant fluid retention develops, evaluate the patient to determine the cause, such as OPSYNVI® or underlying heart failure, and the possible need to discontinue OPSYNVI®.

OPSYNVI®启动后监测液体滞留迹象。如果出现临床上显着的液体潴留，请评估患者以确定原因，例如OPSYNVI®或潜在的心力衰竭，以及可能需要停用OPSYNVI®。

Combination With Other PDE5 Inhibitors

与其他PDE5抑制剂联合使用

Tadalafil, a PDE5 inhibitor and a component of OPSYNVI®, is also indicated for erectile dysfunction.  Instruct patients taking OPSYNVI® tablets not to take other PDE5 inhibitors.

他达拉非是一种PDE5抑制剂和OPSYNVI®的成分，也适用于勃起功能障碍。指导服用OPSYNVI®片剂的患者不要服用其他PDE5抑制剂。

Decreased Sperm Counts and Prolonged Erection

精子数量减少和勃起时间延长

Macitentan may have an adverse effect on spermatogenesis. Counsel men about potential effects on fertility.

马西替坦可能对精子发生有不利影响。建议男性注意对生育能力的潜在影响。

There have been reports of prolonged erections greater than 4 hours and priapism (painful erections greater than 6 hours in duration) for PDE5 inhibitors like tadalafil. Patients with conditions that might predispose them to priapism, or in patients with anatomical deformation of the penis are at an increased risk.

有报道称，他达拉非等PDE5抑制剂的勃起时间延长超过4小时，阴茎异常勃起（持续时间超过6小时的痛苦勃起）。患有可能导致阴茎异常勃起的疾病的患者，或阴茎解剖变形的患者的风险增加。

Patients who have an erection lasting greater than 4 hours, whether painful or not, should seek emergency medical attention. .

勃起持续时间超过4小时的患者，无论是否疼痛，都应寻求紧急医疗护理。

ADVERSE REACTIONS

不良反应

The most common adverse reactions (occurring in ≥ 10% of the OPSYNVI®-treated patients) from the double-blind study data were edema/fluid retention (21%), anemia (19%), and headache/migraine (18%). The incidence of treatment discontinuations due to adverse events among patients receiving OPSYNVI® in the double-blind phase of the study was 8%.

双盲研究数据中最常见的不良反应（发生率≥10%的OPSYNVI®治疗患者）是水肿/体液潴留（21%），贫血（19%）和头痛/偏头痛（18%）。在研究的双盲阶段，接受OPSYNVI®治疗的患者因不良事件而中断治疗的发生率为8%。

The most frequent adverse reactions leading to discontinuation were anemia and hemoglobin decreased (2% grouped) and peripheral edema and peripheral swelling (2% grouped).  .

导致停药的最常见不良反应是贫血和血红蛋白降低（2%组）以及外周水肿和外周肿胀（2%组）。

DRUG INTERACTIONS

药物相互作用

Nitrates: Administration of nitrates within 48 hours after the last dose of OPSYNVI® is contraindicated.

硝酸盐：禁止在最后一剂OPSYNVI®后48小时内服用硝酸盐。

Strong CYP3A4 Inducers: Strong inducers of CYP3A4, such as rifampin, significantly reduce macitentan exposure. Use of OPSYNVI® with strong CYP3A4 inducers should be avoided.

强CYP3A4诱导剂：CYP3A4的强诱导剂，如利福平，可显着减少马西替坦的暴露。应避免使用具有强CYP3A4诱导剂的OPSYNVI®。

Strong CYP3A4 Inhibitors: Concomitant use of strong CYP3A4 inhibitors like ketoconazole, increases exposure to both macitentan and tadalafil. Avoid concomitant use of OPSYNVI® with strong CYP3A4 inhibitors such as ritonavir, ketoconazole and itraconazole. Use other PAH treatment options when strong CYP3A4 inhibitors are needed. .

强效CYP3A4抑制剂：同时使用强效CYP3A4抑制剂（如酮康唑）会增加对马西替坦和他达拉非的暴露。避免同时使用OPSYNVI®和强效CYP3A4抑制剂，如利托那韦、酮康唑和伊曲康唑。当需要强CYP3A4抑制剂时，使用其他PAH治疗选择。

Moderate Dual or Combined CYP3A4 and CYP2C9 Inhibitors:

中度双重或联合CYP3A4和CYP2C9抑制剂：

Concomitant use of moderate dual inhibitors of CYP3A4 and CYP2C9 such as fluconazole, is predicted to increase macitentan exposure approximately 4-fold. Avoid concomitant use of OPSYNVI® with moderate dual inhibitors of CYP3A4 and CYP2C9 (such as fluconazole and amiodarone).

预计同时使用CYP3A4和CYP2C9的中度双重抑制剂（如氟康唑）会使马西替坦的暴露量增加约4倍。避免同时使用OPSYNVI®和CYP3A4和CYP2C9的中度双重抑制剂（如氟康唑和胺碘酮）。

Concomitant treatment of both a moderate CYP3A4 inhibitor and moderate CYP2C9 inhibitor with OPSYNVI® should be avoided.

应避免同时使用OPSYNVI®治疗中度CYP3A4抑制剂和中度CYP2C9抑制剂。

Alpha-Blockers: PDE5 inhibitors, including tadalafil, and alpha-adrenergic blocking agents are both vasodilators with blood-pressure lowering effects. Therefore, the combination of OPSYNVI® and doxazosin is not recommended.

α受体阻滞剂：PDE5抑制剂（包括他达拉非）和α肾上腺素能阻滞剂都是具有降压作用的血管扩张剂。因此，不建议使用OPSYNVI®和多沙唑嗪的组合。

Antihypertensives: PDE5 inhibitors, including tadalafil, are mild systemic vasodilators. Small reductions in blood pressure occurred following coadministration of tadalafil with selected antihypertensive medications compared with placebo.

抗高血压药：PDE5抑制剂，包括他达拉非，是轻度全身血管扩张剂。与安慰剂相比，他达拉非与选定的抗高血压药物合用后血压略有下降。

Alcohol: Substantial consumption of alcohol in combination with OPSYNVI® can increase the potential for orthostatic signs and symptoms, including increase in heart rate, decrease in standing blood pressure, dizziness, and headache.

酒精：大量饮酒与OPSYNVI®联合使用会增加立位体征和症状的可能性，包括心率增加，血压下降，头晕和头痛。

USE IN SPECIFIC POPULATIONS

在特定人群中使用

Pregnancy

怀孕

OPSYNVI® is contraindicated during pregnancy. Macitentan, a component of OPSYNVI®, may cause embryo-fetal toxicity, including birth defects and fetal death, when administered to a pregnant female.

OPSYNVI®在怀孕期间禁用。Macitentan是OPSYNVI®的一种成分，当给孕妇服用时，可能会导致胚胎-胎儿毒性，包括出生缺陷和胎儿死亡。

If the patient becomes pregnant while taking this drug, advise the patient of the risk to a fetus.

如果患者在服用该药物时怀孕，请告知患者胎儿的风险。

Lactation

哺乳期

There are no data on the presence of tadalafil, macitentan, and/or their metabolites in human milk, the effects on the breastfed infant, or the effect on milk production.  Because of the potential for serious adverse reactions in breastfed infants from OPSYNVI®, advise women not to breastfeed during treatment with OPSYNVI®..

没有关于母乳中他达拉非，马西替坦和/或其代谢物的存在，对母乳喂养婴儿的影响或对产奶量的影响的数据。由于OPSYNVI®母乳喂养的婴儿可能会产生严重的不良反应，因此建议女性在使用OPSYNVI®治疗期间不要母乳喂养。

Females and Males of Reproductive Potential

生殖潜力的女性和男性

Pregnancy Testing: Verify the pregnancy status of females of reproductive potential prior to initiating OPSYNVI®, monthly during treatment and one month after stopping treatment with OPSYNVI®. The patient should contact her physician immediately for pregnancy testing if onset of menses is delayed or pregnancy is suspected.

妊娠测试：在开始使用OPSYNVI®之前，在治疗期间每月以及停止使用OPSYNVI®治疗后一个月，验证具有生殖潜力的女性的妊娠状况。如果月经延迟或怀疑怀孕，患者应立即联系医生进行妊娠检测。

If the pregnancy test is positive, the physician and patient must discuss the risks to her, the pregnancy, and the fetus..

如果妊娠试验呈阳性，医生和患者必须讨论对她、怀孕和胎儿的风险。

Contraception: Female patients must choose one highly effective form of contraception (intrauterine devices [IUD]), contraceptive implants or tubal sterilization) or a combination of methods (hormone method with a barrier method or two barrier methods) during treatment with OPSYNVI® and for 1 month after treatment with OPSYNVI®.

避孕：女性患者在使用OPSYNVI®治疗期间和使用OPSYNVI®治疗后1个月内，必须选择一种高效的避孕方式（宫内节育器（IUD）），避孕植入物或输卵管绝育）或多种方法（激素法加屏障法或两种屏障法）的组合。

If a partner's vasectomy is the chosen method of contraception, a hormone or barrier method must be used along with this method..

如果伴侣的输精管切除术是选择的避孕方法，则必须使用激素或屏障方法。

Male Infertility: Based on findings in animals, macitentan may impair fertility in males of reproductive potential. There have been no studies evaluating the effect of tadalafil on fertility in men or women.

男性不育：根据动物的研究结果，马西替坦可能会损害具有生殖潜力的男性的生育能力。目前还没有研究评估他达拉非对男性或女性生育能力的影响。

Pediatric Use

儿科使用

The safety and efficacy of OPSYNVI® in children has not been established.

OPSYNVI®在儿童中的安全性和有效性尚未确定。

Renal Impairment

肾功能损害

The use of OPSYNVI® is not recommended in patients undergoing dialysis. Avoid use of OPSYNVI® in patients with severe renal impairment (creatinine clearance 15-29 mL/min).

不建议接受透析的患者使用OPSYNVI®。避免在严重肾功能不全（肌酐清除率15-29 mL/min）的患者中使用OPSYNVI®。

Hepatic Impairment

肝损害

OPSYNVI® must not be initiated in patients with severe hepatic impairment, or clinically significant elevated hepatic aminotransferases (> 3 × ULN).

OPSYNVI®不得用于严重肝功能损害或临床上显着升高的肝氨基转移酶（>3×ULN）患者。

Please read Important Safety Information and full Prescribing Information, including Boxed WARNING, for OPSYNVI®.

请阅读OPSYNVI®的重要安全信息和完整处方信息，包括盒装警告。

About Johnson & JohnsonAt Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity.

关于强生公司强生公司， 我们相信健康就是一切。我们在医疗创新方面的优势使我们能够建立 预防、治疗和治愈复杂疾病的世界， 在那里治疗更聪明，侵入性更小，并且 解决方案是针对个人的。通过我们在创新医学和医学技术方面的专业知识，我们拥有独特的优势，可以在今天的所有医疗保健解决方案中进行创新，以实现明天的突破，并深刻影响人类的健康。

Learn more at https://www.jnj.com/ or at www.janssen.com/johnson-johnson-innovative-medicine. Follow us at @JanssenUS and @JNJInnovMed. Janssen Research & Development, LLC and Actelion Pharmaceuticals US, Inc., are both Johnson & Johnson companies..

了解更多信息，请访问https://www.jnj.com/或访问www.janssen.com/johnson-johnson-innovative-medicine。请访问@JanssenUS和@JNJInnovMed。Janssen Research&Development，LLC和Actelion Pharmaceuticals US，Inc.都是强生公司。