新型结核病药物SIRTURO((Bedaquiline 双芳基喹啉类抗结核药)-是40余年来首次采用新型作用机制治疗肺部耐多药结核病的药物 【商 品 名】Sirturo Tablets 【英 文 名】Bedaquiline 【中 文 名】贝达喹啉片 【批准时间】2012年12月28日 【用药方式】口服 【原研公司】Janssen Therapeutics 【作用机理】Bedaquiline是一种diarylquinoline抗分枝杆菌药 【适 应 症】Sirturo是一种diarylquinoline抗分枝杆菌药，适用于作为有肺多药耐药性结核(MDR-TB)成年(≥18岁)联合治疗的一部分，当一个有效的治疗方案不能以其他方式提供贮备Sirturo使用。Sirturo不适用为治疗潜伏，肺外或药物敏感结核。 【剂型和规格】100mg/片 【剂量和给药方法】每天1次400mg，共2周；然后每周3次200mg，共22周。与水整吞服Sirturo片。 【警告和注意事项】 （1）用Sirturo可能发生QT延长。定期监视ECG。 （2）如发生显著室性心律失常或QTcF间期 > 500ms终止服用Sirturo。 （3）使用延长QT间期药物可致另外QT延长。更频繁监视ECG。 （4）使用Sirturo曾报道肝相关不良药物反应。监视肝相关实验室检验。 （5）不遵守治疗方案可能导致药效失败或耐药性。 【不良反应】 （1）报道的最常见不良反应（≥10%）是恶心，关节痛，和头痛。 （2）在≥10%的另外不良事件和频率较高于安慰剂治疗组是咯血和胸痛。 【药物相互作用】 （1）避免全身性强CYP3A4诱导剂与Sirturo使用。 （2）避免全身性强CYP3A4抑制剂与Sirturo连续使用多于14天除非获益升高风险。建议临床监视Sirturo相关不良反应。 【特殊人群中使用】 （1）在有轻度至中度肾受损或患者有轻度至中度肝受损患者中无需调整剂量。 （2）有严重肾受损患者谨慎使用。 （3）在有严重肝受损患者谨慎使用和只有当获益胜过风向：建议临床监视Sirturo相关不良反应。 【关于肺结核】 据世界卫生组织报道，目前全球有近1/3的人已感染结核杆菌，也就是20亿人口感染了结核菌。全球有活动性肺结核病人约2000万，每年新发结核病人约 800-1000万，每年约有300万人死于结核病。结核病已成为全世界成人因传染病而死亡的主要疾病之一。我国是全球22个结核病高负担国家之一，活动性肺结核病人数居世界第二位。 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. Download a comprehensive resource on SIRTURO® (bedaquiline) tablets 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%). https://www.medicines.org.uk/emc/medicine/29644 http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm333695.htm