2019年8月14日,美国FDA批准由非盈利组织全球结核病药物开发联盟（TB Alliance）开发的pretomanid上市，与贝达喹啉（bedaquiline）和利奈唑胺（linezolid）联用，治疗特定高度耐药肺结核（TB）患者。这是近40年来FDA批准的第三款抗肺结核新药，也是第一款由非盈利组织开发并且上市的肺结核新药。
由于细菌耐药性的不断增加，多药耐药TB（multidrug-resistant TB）和广泛耐药TB（extensively drug-resistant TB）已经成为威胁人类健康的重大隐患。根据世界卫生组织的统计，在2016年，世界范围内有49万名新多药耐药TB患者，其中一小部分为广泛耐药TB患者。这些患者对多种疗法不耐受或者产生耐药性，因此治疗选择非常有限。目前大多数广泛耐药TB患者可能需要接受多达8种抗生素的治疗，疗程长达18个月或更长。根据WHO的估计，对广泛耐药TB患者治疗的成功率大约为34%。
Pretomanid是一种新化学实体。它与贝达喹啉和利奈唑胺构成的组合疗法的疗效在名为Nix-TB的关键性临床试验中获得了证明。参加这一试验的109名患者包括广泛耐药性TB患者，和对已有疗法不耐受或无反应的多重耐药性患者。试验结果表明，在接受治疗6个月之后，这一组合疗法的成功率达到89%，显著高于治疗广泛耐药TB患者的历史成功率。
耐药感染是公共卫生机构面对的重大挑战，”FDA常务副局长Amy Abernethy博士表示：“开发创新疗法对解决全球患者的健康需求非常重要。因此，我们聚焦于促进安全有效的创新疗法的开发，为抗击危及生命的感染的患者提供更多治疗选择。这一批准是FDA抗菌和抗真菌药物有限人口途径（Limited Population Pathway for Antibacterial and Antifungal Drugs）下批准的第二款新药。这一途径旨在激励针对缺乏有效疗法的传染病的新药开发。我们希望，能够继续看到更多抗生素的开发，治疗具有未竟医疗需求的有限人群罹患的严重感染。”
Generic name: pretomanid
Dosage form: Tablets
Company: TB Alliance
Treatment for: Tuberculosis, Resistant
Pretomanid is a nitroimidazooxazine antimycobacterial indicated for use in combination with bedaquiline and linezolid (the BPaL regimen) for the treatment of adults with pulmonary extensively drug resistant (XDR), treatment-intolerant or nonresponsive multidrug-resistant (MDR) tuberculosis (TB).
Limitations of Use:
Pretomanid Tablets are not indicated for patients with:
Drug-sensitive (DS) tuberculosis
Latent infection due to Mycobacterium tuberculosis
Extra-pulmonary infection due to Mycobacterium tuberculosis
MDR-TB that is not treatment-intolerant or non-responsive to standard therapy
Safety and effectiveness of Pretomanid Tablets have not been established for its use in combination with drugs other than bedaquiline and linezolid as part of the recommended dosing regimen.
DOSAGE AND ADMINISTRATION
Pretomanid Tablets must be administered only as part of a regimen in combination with bedaquiline and linezolid.
Pretomanid 200 mg orally once daily for 26 weeks.
Bedaquiline 400 mg orally once daily for 2 weeks followed by 200 mg 3 times per week, with at least 48 hours between doses, for 24 weeks for a total of 26 weeks.
Linezolid 1,200 mg daily orally for up to 26 weeks, with dose adjustments for known linezolid toxicities.
IMPORTANT SAFETY INFORMATION
Contraindications
Pretomanid Tablets used in combination with bedaquiline and linezolid are contraindicated in patients for whom bedaquiline and/or linezolid is contraindicated.
Warnings and Precautions
Hepatic adverse reactions were reported with the use of the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid. Monitor symptoms and signs and liver‑related laboratory tests. Interrupt treatment with the entire regimen if evidence of liver injury occurs.
Myelosuppression was reported with the use of the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid. Monitor complete blood counts. Decrease or interrupt linezolid dosing if significant myelosuppression develops or worsens.
Peripheral and optic neuropathy were reported with the use of the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid. Monitor visual function. Obtain an ophthalmologic eva luation if there are symptoms of visual impairment. Decrease or interrupt linezolid dosing if neurop |
