Altcheh Jaime, Grossmann Ulrike, Stass Heino, Springsklee Martin, Garcia-Bournissen Facundo
Hospital de Niños Ricardo Gutiérrez and Instituto Multidisciplinario de Investigacion en Patologias Pediatricas (IMIPP), CONICET-GCBA, Buenos Aires, Argentina.
Bayer AG, Research & Development, Clinical Development & Operations, Acute & Chronic Care & Pediatrics, Berlin, Germany.
PLoS Negl Trop Dis. 2025 Feb 25;19(2):e0012849. doi: 10.1371/journal.pntd.0012849. eCollection 2025 Feb.
Nifurtimox has been used for over 50 years to treat patients with Chagas disease, a potentially life-threatening neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi. Without effective antitrypanosomal treatment, the infection can persist and progress to a chronic, often debilitating, clinical form. Migration and urbanization, as well as the shifting distribution of the parasite's insect vector, have contributed to the emergence of Chagas disease as a global health threat. Administration of nifurtimox involves adjusting the dose for age and body weight. Particularly for children, this often requires the previously available 120 mg tablet to be divided manually, which could be problematic. To address this challenge, a new formulation tablet of nifurtimox was developed. Available in two dose strengths, 30 mg and 120 mg, the new formulation tablets contain a functional score line to facilitate accurate division. In addition, the formulation now allows rapid and easy dispersion in water to form a slurry for use by patients with difficulty swallowing tablets. These features enable more accurate body-weight-based and age-appropriate dosing and administration, which should prove beneficial for younger patients, including newborns and babies with a body weight ≥2.5 kg. Development of the new formulation nifurtimox tablets was guided by substantially updating pharmacological and clinical knowledge of the drug to meet current standards and regulatory requirements. This was achieved by conducting a substantial array of additional non-clinical and clinical studies to better understand and characterize clinically relevant aspects of nifurtimox pharmacokinetics. The efficacy and safety of the new tablet in children with Chagas disease was subsequently demonstrated in a large prospective randomized clinical trial with prolonged follow-up. In the present paper, we review key findings that contributed to the successful clinical development of the new formulation nifurtimox tablet, the availability of which redefines the treatment of young patients with Chagas disease.
硝呋替莫已被用于治疗恰加斯病患者50多年，恰加斯病是一种由原生动物寄生虫克氏锥虫引起的潜在威胁生命的被忽视热带病。如果没有有效的抗锥虫治疗，感染可能会持续并发展为慢性临床形式，通常会使人虚弱。移民和城市化以及寄生虫昆虫媒介分布的变化，导致恰加斯病成为全球健康威胁。服用硝呋替莫需要根据年龄和体重调整剂量。特别是对于儿童，这通常需要将以前可用的120毫克片剂手动分割，这可能会有问题。为应对这一挑战，开发了一种新的硝呋替莫制剂片剂。新制剂片剂有30毫克和120毫克两种剂量规格，含有一条功能性刻痕线，便于准确分割。此外，该制剂现在可以在水中快速轻松地分散形成混悬液，供吞咽片剂有困难的患者使用。这些特性能够实现更准确的基于体重和适合年龄的给药，这对年轻患者，包括体重≥2.5千克的新生儿和婴儿应该是有益的。新制剂硝呋替莫片剂的开发以大幅更新该药物的药理学和临床知识为指导，以满足当前标准和监管要求。这是通过进行大量额外的非临床和临床研究来实现的，以便更好地理解和描述硝呋替莫药代动力学的临床相关方面。随后，在一项长期随访的大型前瞻性随机临床试验中证明了新片剂对恰加斯病儿童的疗效和安全性。在本文中，我们回顾了有助于新制剂硝呋替莫片剂成功临床开发的关键发现，其可用性重新定义了恰加斯病年轻患者的治疗方法。
