What is the interaction between rifapentine (Rifapentine) and moxifloxacin (Moxifloxacin)?

Rifapentine-Moxifloxacin Interaction

Rifapentine significantly reduces moxifloxacin plasma concentrations by approximately 17-31% through hepatic enzyme induction, but this combination is clinically effective and recommended as part of the 4-month tuberculosis treatment regimen for eligible patients. 1

Mechanism of Interaction

• Rifapentine is a potent inducer of multiple hepatic enzymes (similar to rifampin), which increases the metabolism of co-administered drugs including moxifloxacin 1
• Moxifloxacin AUC₀₋₂₄ decreases by 17.2% when co-administered with rifapentine, with the half-life dropping from 11.1 to 8.9 hours 2
• The reduction in moxifloxacin concentrations can be as high as 31% in some studies, particularly with repeated rifapentine dosing 3
• Rifapentine also demonstrates autoinduction, with its own AUC₀₋₄₈ decreasing by 20.3% after seven thrice-weekly doses 2

Clinical Significance and Recommendations

Despite the pharmacokinetic interaction, the rifapentine-moxifloxacin combination is highly effective and CDC-recommended:

• The 4-month daily regimen (rifapentine 1200 mg + moxifloxacin 400 mg + isoniazid + pyrazinamide) is as effective as the standard 6-month regimen for drug-susceptible pulmonary tuberculosis in patients ≥12 years old 1
• This regimen was validated in Study 31/A5349, a phase 3 noninferiority trial with 2,516 participants that confirmed equivalent cure rates 1
• The WHO conditionally recommended this 4-month regimen in May 2022 for eligible patients with pulmonary drug-susceptible TB 1

Dosing Considerations

Standard dosing remains unchanged despite the interaction:

• Rifapentine: 1200 mg daily (approximately 15 mg/kg for patients ≥40 kg) 1
• Moxifloxacin: 400 mg daily (standard dose maintained) 1
• All medications should be administered with food to optimize absorption 1
• Treatment consists of 8 weeks intensive phase (all 4 drugs) followed by 9 weeks continuation phase (rifapentine, moxifloxacin, isoniazid only) for a total of 119 doses 1

Monitoring Requirements

Close monitoring is essential when using this combination:

• Monthly sputum cultures until two consecutive specimens are negative 1
• Repeat drug susceptibility testing if cultures remain positive after 8 weeks of treatment 1
• Monitor liver enzymes (ALT, AST, bilirubin, alkaline phosphatase), platelet count, creatinine, and electrolytes at baseline, week 4, week 8, week 12, and end of treatment 1
• Drug interactions involving rifapentine are similar to rifampin and require careful medication review 1

Important Caveats

Specific populations where this regimen should NOT be used:

• Patients with known or suspected drug resistance to any component of the regimen 1
• HIV-infected patients with CD4 counts <100 cells/μL 1
• HIV-infected patients on non-efavirenz-based antiretroviral therapy (due to additional drug interactions) 1
• Pregnant women, young children, and patients with extrapulmonary TB (insufficient efficacy data) 1
• Patients who received >5 doses of any regimen drug in the preceding 30 days 1

Clinical Bottom Line

The pharmacokinetic interaction between rifapentine and moxifloxacin is real and measurable, but the clinical efficacy of the combination is proven. The reduced moxifloxacin concentrations (median AUC₀₋₂₄ of 28.0 mcg*h/mL with daily rifapentine) 4 are still sufficient for bactericidal activity when combined with high-dose rifapentine 4, 5. Do not adjust doses to compensate for the interaction—use the standard recommended doses as the regimen was studied and validated with these expected lower moxifloxacin levels. 1