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Rifampin, isoniazid, pyrazinamide, ethambutol
This is a fixed-dose combination of four first-line anti-tuberculosis drugs that work synergistically to inhibit bacterial cell wall synthesis and mycolic acid production, killing Mycobacterium tuberculosis.
This is a fixed-dose combination of four first-line anti-tuberculosis drugs that work synergistically to inhibit bacterial cell wall synthesis and mycolic acid production, killing Mycobacterium tuberculosis. Used for Tuberculosis (drug-susceptible, pulmonary and extrapulmonary), Tuberculosis treatment in treatment-naïve patients.
At a glance
| Generic name | Rifampin, isoniazid, pyrazinamide, ethambutol |
|---|---|
| Also known as | Systematic Empiric treatment |
| Sponsor | ANRS, Emerging Infectious Diseases |
| Drug class | Anti-tuberculosis agent (fixed-dose combination) |
| Target | Multiple: RNA polymerase (rifampin), mycolic acid synthesis (isoniazid), arabinosyl transferases (ethambutol), pyrazinamidase/nicotinamidase (pyrazinamide) |
| Modality | Small molecule |
| Therapeutic area | Infectious Disease |
| Phase | FDA-approved |
Mechanism of action
Rifampin inhibits bacterial RNA polymerase, isoniazid inhibits mycolic acid synthesis in the cell wall, pyrazinamide disrupts cellular metabolism and energy production, and ethambutol inhibits arabinosyl transferases involved in cell wall biosynthesis. The combination targets multiple pathways simultaneously to prevent resistance and achieve rapid bactericidal activity against tuberculosis.
Approved indications
- Tuberculosis (drug-susceptible, pulmonary and extrapulmonary)
- Tuberculosis treatment in treatment-naïve patients
Common side effects
- Hepatotoxicity
- Peripheral neuropathy (isoniazid-related)
- Hyperuricemia (pyrazinamide-related)
- Optic neuritis (ethambutol-related)
- Gastrointestinal disturbance
- Rash
- Drug-drug interactions (rifampin-mediated)
Key clinical trials
- Safety and Tolerability of Metformin in People With Tuberculosis (TB) and Human Immunodeficiency Virus (HIV) (PHASE2)
- Shortened Regimen for Drug-susceptible TB in Children (PHASE3)
- Trial of Novel Regimens for the Treatment of Pulmonary Tuberculosis (PHASE2)
- AIPH-TB: AI-Optimised Pyrazinamide-Hydroxychloroquine vs Standard RIPE for Drug-Sensitive Pulmonary Tuberculosis - A Phase II RCT (PHASE2)
- Phase 2a Trial of Alpibectir Plus Ethionamide for Tuberculosis Meningitis (PHASE2)
- Digitally Facilitated, Integrated Community and Facility-Based Interventions: The HEART-TB Trial Protocol (NA)
- Ultra-Short Course Bedaquiline, Clofazimine, Pyrazinamide and Delamanid Versus Standard Therapy for Drug-Susceptible TB (PHASE2)
- Asymptomatic TB With Innovative Modified Short-course Regimens (PHASE4)
Primary sources
Every claim on this page is sourced from regulatory or scientific primary sources. See our editorial policy for full methodology.
| Source | Used for |
|---|---|
| ClinicalTrials.gov | Trial enrolment, design, endpoints, results |
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