Clofazimine Applications in Tuberculosis Treatment

Clofazimine, originally developed in the 1950s, has re-emerged as a key component of modern tuberculosis therapy, particularly in drug-resistant forms of the disease. Its unique riminophenazine structure confers potent antimycobacterial activity against multidrug-resistant and extensively drug-resistant strains. Characterised by extensive tissue accumulation and a long elimination half-life, clofazimine contributes to treatment shortening when combined with companion drugs. Despite uncertain mechanisms of action, evidence points to both direct bactericidal effects and immunomodulatory properties. Global interest has intensified around optimising dosing strategies, mitigating adverse events such as skin pigmentation and cardiac repolarisation changes, and developing novel formulations for targeted delivery. Recent efforts have explored innovative short-course regimens, paediatric dosing guidance, and inhalable microparticle platforms to improve efficacy, safety and patient adherence on a global scale.

Research from Nature Portfolio

An output-driven optimisation platform has identified combination regimens that exclude conventional first-line agents, yielding markedly accelerated clearance of Mycobacterium tuberculosis in murine models. By systematically screening billions of potential drug-dose permutations in an in vitro macrophage infection model, researchers refined two regimens that achieved relapse-free cure in mice in 25% of the time required by the standard regimen. These new combinations, which omit isoniazid, rifampicin, fluoroquinolones and injectable aminoglycosides, hold promise for treating multidrug-resistant and extensively drug-resistant tuberculosis in humans, aiming to reduce treatment duration and the risk of poor adherence.

Clofazimine Applications in Tuberculosis Treatment publication trend

The graph below shows the total number of articles in clofazimine applications in tuberculosis treatment across all publications each year (not limited to Nature Index journals).

Technical terms

Drug-resistant tuberculosis: Tuberculosis caused by strains of Mycobacterium tuberculosis that are not susceptible to one or more first-line antitubercular agents.

Sputum culture conversion: The change from a positive to a negative culture for Mycobacterium tuberculosis in expectorated sputum samples, indicating microbiological response to therapy.

Pharmacokinetics: The study of the processes of drug absorption, distribution, metabolism and excretion that determines drug concentrations over time.

QTcF interval: The Fridericia-corrected QT interval on an electrocardiogram, used to assess drug-induced prolongation of cardiac repolarisation.

Dry powder inhalable formulation: A solid aerosol formulation designed for pulmonary administration to deliver drugs directly to the lungs.

References

1. Clofazimine: A journey of a drug. Biomedicine & Pharmacotherapy (2023).
2. Drug regimens identified and optimized by output-driven platform markedly reduce tuberculosis treatment time. Nature Communications (2017).
3. Efficacy and safety of an innovative short-course regimen containing clofazimine for treatment of drug-susceptible tuberculosis: a clinical trial. Emerging Microbes & Infections (2023).
4. Pharmacokinetics and cardiac safety of clofazimine in children with rifampicin-resistant tuberculosis. Antimicrobial Agents and Chemotherapy (2023).
5. Design of Experiment (DoE) Approach for Developing Inhalable PLGA Microparticles Loaded with Clofazimine for Tuberculosis Treatment. Pharmaceuticals (2024).