Weight-Based Dosing of Fixed-Dose Combination Anti-Tuberculosis Medications for Pulmonary TB
For adults with pulmonary tuberculosis, fixed-dose combination tablets should be dosed based on body weight using the FDA-approved Rifater formulation during the 2-month intensive phase: patients ≤44 kg receive 4 tablets daily, 45-54 kg receive 5 tablets daily, and ≥55 kg receive 6 tablets daily, with all tablets administered as a single daily dose. 1
Available FDC Formulations and Composition
- Rifater (the 4-drug FDC) contains rifampin 120 mg + isoniazid 50 mg + pyrazinamide 300 mg per tablet 1
- Rifamate (the 2-drug FDC) contains rifampin 300 mg + isoniazid 150 mg per capsule, dosed as 2 capsules daily during the continuation phase 1
- These are the only two FDA-approved fixed-dose combinations available in the United States 1
Weight-Based Dosing Algorithm for Rifater (Intensive Phase)
The weight-based dosing for the 4-drug FDC during the initial 2-month intensive phase is:
- ≤44 kg body weight: 4 tablets daily 1
- 45-54 kg body weight: 5 tablets daily 1
- ≥55 kg body weight: 6 tablets daily 1
Critical Administration Requirements
- All tablets must be taken together as a single daily dose—never split throughout the day 1
- The intensive phase lasts for 56 doses over 8 weeks 1
- After the intensive phase, transition to Rifamate (2-drug FDC) for the 4-month continuation phase 1
Individual Drug Dosing Targets Achieved by FDC
The weight-based FDC dosing achieves the following approximate individual drug doses:
- Isoniazid: 5 mg/kg daily (maximum 300 mg) 2
- Rifampin: 10 mg/kg daily (maximum 600 mg) 3
- Pyrazinamide: 15-30 mg/kg daily (maximum 2 g) 4
- Ethambutol: Should be added separately if needed, as Rifater does not contain ethambutol 5
Important Contraindications to FDC Use
Fixed-dose combinations should NOT be used in the following situations 1:
- Intermittent (twice or thrice weekly) dosing regimens
- Pregnancy (requires individualized dosing)
- Renal insufficiency (requires dose adjustments)
- Hepatic disease (requires modified regimens)
Advantages of FDC Over Separate Tablets
- Prevents inadvertent monotherapy, which is the primary cause of acquired drug resistance 1
- Reduces pill burden from 4-6 separate tablets to a single formulation 1
- Improves adherence and reduces medication errors 1
- Simplifies directly observed therapy administration 1
Common Pitfalls to Avoid
- Never use FDCs for intermittent therapy—the dosing is only validated for daily administration 1
- Never split the daily dose—all tablets must be taken together to maintain appropriate pharmacokinetics 1
- Never use FDCs without confirming adequate bioavailability—only use WHO-prequalified or FDA-approved formulations, as many generic FDCs achieve inadequate blood levels 1
- Never continue Rifater beyond 2 months—switch to the 2-drug FDC (Rifamate) for the continuation phase 1
Monitoring Requirements During FDC Therapy
- Baseline liver function tests before initiating treatment 1
- Weekly clinical assessments for the first 2 weeks, then every 2 weeks for the first 2 months 1
- Monthly clinical assessments thereafter for adverse effects 1
- Sputum smear microscopy at 2 months (end of intensive phase), 5 months, and end of treatment 5
Special Considerations for Weight Extremes
- For patients <40 kg, individual drug dosing may be more appropriate than FDCs to avoid underdosing 6
- For patients >90 kg, consider therapeutic drug monitoring as standard FDC dosing may result in suboptimal drug levels 7
- The British Thoracic Society recommends rifampicin 450 mg for patients <50 kg and 600 mg for patients >50 kg, which may require adjustment beyond standard FDC dosing 5