Why do we use 100 mg of clofazimine in TB and NTM treatment?

Current tuberculosis and non-tuberculous mycobacterial disease guidelines recommend the use of clofazimine in a 100 mg once-daily dose. The rationale behind this exact dose is not provided. I performed a literature review to determine the reasoning behind the current dosing regimen. The current 100 mg once-daily dose of clofazimine stems from a deliberate attempt to find the minimum effective daily dose in leprosy treatment, driven by efficacy, economical and toxicity considerations. While this dose is safe, economical and practical, a higher dose with a loading phase may add relevant efficacy and treatment-shortening potential to both tuberculosis and non-tuberculous mycobacterial disease treatment. We need to revisit dose-response and maximum tolerated dose studies to get the best out of this drug, while continuing efforts to generate more active r-iminophenazine molecules that accumulate less in skin and intestinal tissues and have pharmacokinetic properties that do not require loading doses.