Substituting Rifampicin with Moxifloxacin to Avoid Voriconazole Interactions: Not Recommended
No, this substitution is incorrect and potentially dangerous—rifampicin must remain the backbone of tuberculosis treatment for drug-susceptible TB, and voriconazole concentrations will be subtherapeutic with ANY rifamycin, making this substitution futile while compromising TB treatment efficacy. 1, 2
Why This Strategy Fails on Multiple Levels
The Voriconazole Problem Persists
- Voriconazole concentrations become subtherapeutic with ALL rifamycins, not just rifampicin. 1 This includes rifabutin and rifapentine, so switching between rifamycins does not solve the antifungal problem.
- The ATS/CDC/IDSA guidelines explicitly state that itraconazole, ketoconazole, and voriconazole concentrations may be subtherapeutic with any of the rifamycins. 1
- Fluconazole is the only azole that can be used with rifamycins, though the dose may need to be increased. 1
Moxifloxacin Is Not an Equivalent Substitute
- Rifampicin is irreplaceable as the backbone of first-line TB therapy due to its unique sterilizing activity against dormant bacilli. 2 Moxifloxacin lacks this critical property.
- Moxifloxacin-containing shortened regimens have demonstrated significantly higher relapse rates compared to rifampicin-based regimens. 2
- The ATS guidelines recommend continuing rifampicin-based treatment as the standard of care for drug-susceptible TB. 2
The Drug Interaction Creates Additional Problems
- Rifampicin actually DECREASES moxifloxacin concentrations by 31-39% when co-administered, making this combination doubly problematic. 3, 4, 5
- In a study of 19 Indonesian TB patients, co-administration of moxifloxacin with rifampicin resulted in a geometric mean ratio of 0.69 for moxifloxacin AUC (31% reduction). 4
- A Dutch study showed moxifloxacin AUC decreased by 39% when rifampicin was co-administered, with only 65% of patients achieving the target AUC/MIC ratio. 5
When Moxifloxacin IS Appropriate in TB Treatment
Moxifloxacin has specific, limited roles that do NOT include routine substitution for rifampicin:
Isoniazid-Resistant TB
- Add moxifloxacin to a 6-month regimen of rifampicin, ethambutol, and pyrazinamide for isoniazid-resistant TB. 2
Hepatotoxicity from First-Line Agents
- Moxifloxacin can be used as part of a non-hepatotoxic regimen when isoniazid, rifampicin, AND pyrazinamide all cause hepatitis, until liver enzymes normalize. 2, 6
Multidrug-Resistant TB
- Moxifloxacin becomes a core component of MDR-TB regimens. 2
The Correct Approach to This Clinical Dilemma
Prioritize TB Treatment
- TB treatment failure and relapse carry significant morbidity and mortality—do not compromise TB treatment efficacy by removing rifampicin simply to accommodate voriconazole. 2
Alternative Antifungal Strategies
- Switch to fluconazole (the only azole compatible with rifamycins), though you may need to increase the fluconazole dose. 1
- Consider amphotericin B formulations (deoxycholate or liposomal) if fluconazole is inadequate for the fungal infection. 1
- If voriconazole is absolutely essential, consider a non-rifamycin-containing TB regimen only for specific circumstances (e.g., rifampicin intolerance), but this requires expert consultation. 1
Temporal Separation Strategy
- If the fungal infection can be treated sequentially rather than concurrently, complete one treatment course before starting the other.
Critical Pitfalls to Avoid
- Never assume switching between rifamycins solves azole interactions—all rifamycins affect voriconazole. 1
- Never use moxifloxacin as a first-line substitute for rifampicin in drug-susceptible TB—this increases relapse risk. 2
- Never ignore the rifampicin-moxifloxacin interaction—if you must use both, consider higher moxifloxacin doses (600 mg) with therapeutic drug monitoring. 5
- Never compromise TB treatment to accommodate a less critical infection—TB has higher mortality if inadequately treated. 2