4-Month TB Treatment Regimens
Rifapentine-Moxifloxacin Regimen (Preferred 4-Month Option)
The CDC recommends a 4-month daily regimen consisting of 8 weeks of rifapentine, isoniazid, pyrazinamide, and moxifloxacin, followed by 9 weeks of rifapentine, isoniazid, and moxifloxacin for patients aged ≥12 years with drug-susceptible pulmonary tuberculosis. 1
Specific Dosing
Intensive Phase (8 weeks, 56 doses): 1
- Rifapentine 1,200 mg daily
- Moxifloxacin 400 mg daily
- Isoniazid 300 mg daily (with pyridoxine 25-50 mg/day)
- Pyrazinamide: 1,000 mg (40-<55 kg), 1,500 mg (55-75 kg), or 2,000 mg (>75 kg) daily
Continuation Phase (9 weeks, 63 doses): 1
- Rifapentine 1,200 mg daily
- Moxifloxacin 400 mg daily
- Isoniazid 300 mg daily (with pyridoxine)
Total: 119 doses over approximately 4 months 1
Key Implementation Details
- All medications must be administered daily with food, 7 days per week 1
- At least 5 of 7 weekly doses should be given under direct observation 1
- Intensive phase must be completed within 70 days; continuation phase within 84 days of intensive phase completion 1
- Treatment duration is independent of cavitation on chest radiograph 1
Eligibility Criteria
This regimen is appropriate for: 1
- Patients aged ≥12 years with body weight ≥40 kg
- Drug-susceptible pulmonary TB (confirmed or not suspected to be resistant)
- HIV-positive patients with CD4 counts ≥100 cells/μL receiving or planning efavirenz-based ART
This regimen should NOT be used in: 1
- Patients with ALT/AST >3× upper limit of normal or total bilirubin >2.5× upper limit of normal
- Advanced liver disease
- Serum creatinine >2× upper limit of normal or end-stage renal disease
- Plasma potassium <3.5 mEq/L
- Extrapulmonary TB (pleural or lymph node TB only)
- Patients who received >5 doses of isoniazid, rifampin, rifabutin, rifapentine, pyrazinamide, or fluoroquinolones in preceding 30 days
- Patients who received latent TB treatment in preceding 6 months
Evidence Base
This regimen demonstrated non-inferiority to the standard 6-month regimen in the Study 31/A5349 international phase 3 trial involving 2,516 participants, confirming equal efficacy in curing drug-susceptible TB. 1
Standard 4-Month Continuation Phase (Traditional Approach)
For patients using the traditional initial 2-month intensive phase with isoniazid, rifampin, pyrazinamide, and ethambutol, a 4-month continuation phase with isoniazid and rifampin is appropriate for the majority of patients. 1
When 4-Month Continuation Phase is Appropriate
The 4-month continuation phase should be used for: 1
- Patients with non-cavitary pulmonary TB who have negative sputum cultures at 2 months
- HIV-negative patients meeting above criteria
- Patients who received pyrazinamide in the initial phase
When 7-Month Continuation Phase is Required (Total 9 Months)
Extend continuation phase to 7 months in these specific situations: 1
- Cavitary pulmonary TB on initial chest radiograph AND positive sputum culture at 2 months
- Initial phase did not include pyrazinamide
- Once-weekly isoniazid-rifapentine regimen with positive sputum culture at 2 months
Critical Monitoring for 4-Month Regimens
Baseline Requirements for Rifapentine-Moxifloxacin Regimen
Before initiating treatment, obtain: 1
- Sputum for rapid molecular testing, AFB smear, and culture
- Drug susceptibility testing (molecular for isoniazid, pyrazinamide, rifampin, fluoroquinolones; phenotypic DST for rifampin as surrogate for rifapentine, isoniazid, pyrazinamide, moxifloxacin)
- Chest radiograph
- Liver function tests (ALT, AST, bilirubin, alkaline phosphatase)
- Platelet count, creatinine, potassium, calcium, magnesium
- HIV testing
- Hepatitis B and C screening
- Diabetes screening
- Pregnancy testing for persons who might become pregnant
Follow-Up Monitoring
Monthly sputum cultures until two consecutive negatives are documented 1
At weeks 4,8,12, and 17 (end of treatment): 1
- Weight, symptoms, adverse events, adherence assessment
- Liver function tests, platelet count, creatinine, electrolytes (if abnormal at baseline or symptoms develop)
Common Pitfalls to Avoid
- Do not use the rifapentine-moxifloxacin regimen in patients with significant hepatic or renal dysfunction without expert consultation 1
- Do not assume the 4-month regimen is appropriate for all patients—carefully review exclusion criteria 1
- Do not skip baseline drug susceptibility testing—molecular and phenotypic testing is essential before using the rifapentine-moxifloxacin regimen 1
- Do not extend the traditional 4-month continuation phase to 7 months based solely on cavitation—positive culture at 2 months is also required 1
- Do not use the rifapentine-moxifloxacin regimen in patients with recent fluoroquinolone exposure—this may select for resistance 1