← Search & browse all drugs
ANTIINFECTIVES FOR SYSTEMIC USE › ANTIMYCOBACTERIALS › DRUGS FOR TREATMENT OF TUBERCULOSIS › Combinations of drugs for treatment of tuberculosis
rifampicin, pyrazinamide, ethambutol and isoniazid
J04AM06
Forms & Strengths
- Fixed-dose combination (FDC) tablet: Isoniazid 75 mg / Pyrazinamide 400 mg / Rifampicin 150 mg / Ethambutol HCl 275 mg
Adult Dosing
- Weight-based daily dosing (intensive phase of tuberculosis treatment): 37-49 kg: 2 tablets daily; 50-70 kg: 3 tablets daily; >70 kg: 4 tablets daily, administered as a single daily dose on an empty stomach.
Pediatric Dosing
- Not generally recommended for pediatric use as a fixed-dose combination due to fixed ratios and difficulty in precise weight-based titration; individual agents are preferred for children.
Indications
- Initial intensive phase treatment of pulmonary and extrapulmonary tuberculosis caused by Mycobacterium tuberculosis.
Mechanism of Action
- Isoniazid inhibits mycolic acid synthesis; Rifampicin inhibits DNA-dependent RNA polymerase; Pyrazinamide disrupts bacterial cell membrane metabolism and transport; Ethambutol inhibits arabinosyl transferase, impairing cell wall synthesis.
Contraindications
- Hypersensitivity to any of the component drugs
- Acute liver disease
- History of drug-induced hepatic injury from isoniazid, pyrazinamide, or rifampicin
- Severe renal impairment (for ethambutol and pyrazinamide components)
- Concomitant use with saquinavir/ritonavir (due to severe hepatotoxicity with rifampicin)
Adverse Reactions
- Hepatotoxicity (elevated transaminases, clinical hepatitis)
- Peripheral neuropathy (isoniazid)
- Optic neuritis and visual disturbances (ethambutol)
- Hyperuricemia and gout (pyrazinamide)
- Gastrointestinal upset (nausea, vomiting, abdominal pain)
- Orange-red discoloration of body fluids (rifampicin)
- Hypersensitivity reactions and rash
Drug Interactions
- Rifampicin is a potent CYP450 enzyme inducer (decreases efficacy of PIs, NNRTIs, anticoagulants, oral contraceptives, azoles)
- Antacids decrease absorption of isoniazid and rifampicin
- Pyrazinamide may decrease the efficacy of uricosuric agents
- Increased risk of neurotoxicity when isoniazid is used with other neurotoxic agents
Curated Content: Needs Vetting Before Put to Clinical Use