英文药名：SIRTURO(bedaquiline Tablets) 中文药名：贝达喹啉片（双芳基喹啉类抗结核药） 生产厂家：JANSSEN-CILAG GmbH 药品介绍 2013年12月25日，Sirturo (bedaquiline，双芳基喹啉类抗结核药)在欧洲获得批准，成为几十年来进入欧洲市场的新类型结核病(TB)治疗药物之一。欧盟已授予上市许可，做为肺多重耐药(MDR) TB 合并治疗方案的一部分，该病症属孤儿适应症，在欧洲影响大约万分之二的人口。 此前，Sirturo已被指定为孤儿药地位 去年12月，FDA通过加速审批程序批准了Sirturo，这是近四十年来FDA首次批准的抗结核药物，在无其它替代药物可用时作为成人多重耐药的结核（TB）联合治疗的组成部分。 结核病（tuberculosis）是由结核杆菌（Mycobacterium tuberculosis）引发的一种传染性疾病，主要影响肺部。在欧盟，结核病是一种罕见病，据2011年预计数据，结核病在欧盟的发病率约为万分之2.3。耐多药结核病是指至少对异烟肼（ isoniazid）和利福平（rifampicin）耐药的结核病，这2种药物是用于结核病标准治疗中的2种主要的抗结核药物。据估计，在全球范围内，每年发生约45万例耐多药结核病病例，相当于全球每年结核病的5%。 近年来，由于缺乏新的治疗选择，耐药性结核病所导致的公共健康问题迅速增加。耐多药结核病与高的死亡率相关，已构成了严重的公共健康威胁，因为感染了耐药菌株的患者无法获得充分的治疗，并有可能传播感染。 Sirturo则为那些没有其他治疗选择的患者带来了希望。但是，该药也有一些严重的风险，医生应确保合理应用该药物，只适用于对其他抗结核治疗无效的患者。 Sirturo是一类新的抗结核杆菌药物的首个代表。CHMP认为，Sirturo可能有助于应对多耐药结核病在新治疗选择方面远未满足的医疗需求。因此，CHMP建议授予Sirturo有条件上市许可，尽管强生所提供的数据表明，Sirturo的临床利益大于其风险，但这些数据尚不全面。因此，应该就Sirturo的使用开展更多的研究。 包装规格[注：以下产品德国上市包装] ・100mg*24片 ・100mg*188片 生产厂家：JANSSEN-CILAG GmbH SIRTURO® Is the First Medication for Pulmonary MDR-TB With a Novel Mechanism of Action in Over 40 Years INDICATIONS AND USAGE SIRTURO® (bedaquiline) is a diarylquinoline antimycobacterial drug indicated as part of combination therapy in the treatment of adults (≥18 years) with pulmonary multi drug resistant tuberculosis (MDR TB). Reserve SIRTURO® for use when an effective treatment regimen cannot otherwise be provided. Administer SIRTURO® by directly observed therapy (DOT). This indication is approved under accelerated approval based on time to sputum culture conversion. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Limitations of Use Do not use SIRTURO® for the treatment of: •Latent infection due to Mycobacterium tuberculosis •Drug-sensitive tuberculosis •Extrapulmonary tuberculosis •Infections caused by non-tuberculous mycobacteria The safety and efficacy of SIRTURO® in the treatment of HIV-infected patients with MDR-TB have not been established as clinical data are limited. Mechanism of Action •SIRTURO® is the first anti-TB drug to interfere with bacterial energy metabolism. •SIRTURO® specifically inhibits mycobacterial ATP (adenosine 5'-triphosphate) synthase, by binding to subunit c of the enzyme that is essential for the generation of energy in Mycobacterium tuberculosis. IMPORTANT SAFETY INFORMATION WARNINGS: INCREASED MORTALITY; QT PROLONGATION Increased Mortality •An increased risk of death was seen in the SIRTURO® treatment group (9/79, 11.4%) compared to the placebo treatment group (2/81, 2.5%) in one placebo-controlled trial. Only use SIRTURO® when an effective treatment regimen cannot otherwise be provided. QT Prolongation •QT prolongation can occur with SIRTURO®. Use with drugs that prolong the QT interval may cause additive QT prolongation. Monitor ECGs. Discontinue SIRTURO® if significant ventricular arrhythmia or if QTcF interval prolongation of greater than 500 ms develops. Warnings and Precautions Increased Mortality An increased risk of death was seen in the SIRTURO® treatment group. The imbalance in deaths is unexplained. No discernible pattern between death and sputum culture conversion, relapse, sensitivity to other drugs used to treat tuberculosis, HIV status, or severity of disease could be observed. Only use SIRTURO® when an effective treatment regimen cannot otherwise be provided. QT Prolongation SIRTURO® prolongs the QT interval. Obtain an ECG before initiation of treatment, and at least 2, 12, and 24 weeks after starting treatment with SIRTURO®. Obtain serum potassium, calcium, and magnesium at baseline and correct if abnormal. Monitor electrolytes if QT prolongation is detected. SIRTURO® has not been studied in patients with ventricular arrhythmias or recent myocardial infarction. The following may increase the risk for QT prolongation when patients are receiving SIRTURO®: use with other QT prolonging drugs including fluoroquinolones and macrolide antibacterial drugs and the antimycobacterial drug, clofazimine; a history of Torsade de Pointes; a history of congenital long QT syndrome; a history of or ongoing hypothyroidism; a history of or ongoing bradyarrhythmias; a history of uncompensated heart failure; serum calcium, magnesium, or potassium levels below the lower limits of normal If necessary, bedaquiline treatment initiation could be considered in these patients after a favorable benefit risk assessment and with frequent ECG monitoring. Discontinue SIRTURO® and all other QT prolonging drugs if the patient develops clinically significant ventricular arrhythmia or a QTcF interval of greater than 500 ms (confirmed by repeat ECG). If syncope occurs, obtain an ECG to detect QT prolongation. Hepatotoxicity More hepatic-related adverse drug reactions were reported with the use of SIRTURO® plus other drugs to treat tuberculosis compared to other drugs used to treat tuberculosis without the addition of SIRTURO®. Alcohol and other hepatotoxic drugs should be avoided while on SIRTURO®, especially in patients with impaired hepatic function. Monitor symptoms (such as fatigue, anorexia, nausea, jaundice, dark urine, liver tenderness, and hepatomegaly) and laboratory tests (ALT, AST, alkaline phosphatase, and bilirubin) at baseline, monthly while on treatment, and as needed. Test for viral hepatitis and discontinue other hepatotoxic medications if evidence of new or worsening liver dysfunction occurs. Discontinue SIRTURO® if: •aminotransferase elevations are accompanied by total bilirubin elevation greater than two times the upper limit of normal •aminotransferase elevations are greater than eight times the upper limit of normal •aminotransferase elevations are greater than five times the upper limit of normal and persist beyond two weeks Drug Interactions CYP3A4 Inducers/Inhibitors: Bedaquiline is metabolized by CYP3A4 and its systemic exposure and therapeutic effect may therefore be reduced during co-administration with inducers of CYP3A4. Avoid coadministration of strong CYP3A4 inducers such as rifamycins (i.e., rifampin, rifapentine, and rifabutin) or moderate CYP3A4 inducers such as efavirenz. Co-administration of SIRTURO® with strong CYP3A4 inhibitors may increase the systemic exposure to bedaquiline, which could potentially increase the risk of adverse reactions. Therefore, avoid the use of strong CYP3A4 inhibitors used for more than 14 consecutive days while on SIRTURO®, unless the benefit of treatment with the drug combination outweighs the risk. Appropriate clinical monitoring for SIRTURO®-related adverse reactions is recommended. Adverse Reactions Adverse reactions that occurred more frequently than placebo during treatment with SIRTURO® included: nausea (38% vs. 32%), arthralgia (33% vs. 22%), headache (28% vs. 12%), hemoptysis (18% vs. 11%), chest pain (11% vs. 7%), anorexia (9% vs. 4%), transaminases increased (9% vs. 1%), rash (8% vs. 4%), and blood amylase increased (3% vs. 1%). http://www.medicines.org.uk/emc/medicine/29644