A fixed-dose combination (FDC) of two first-line bactericidal antitubercular drugs. Rifampicin is a rifamycin antibiotic that inhibits bacterial DNA-dependent RNA polymerase. Isoniazid is a prodrug activated by bacterial catalase-peroxidase (KatG), inhibiting mycolic acid synthesis in the mycobacterial cell wall. This combination is a cornerstone of the Directly Observed Treatment, Short-course (DOTS) strategy for tuberculosis in India, as recommended by the Revised National Tuberculosis Control Programme (RNTCP), now NTEP (National Tuberculosis Elimination Programme). It is primarily used in the intensive phase of treatment for drug-sensitive pulmonary and extrapulmonary TB.
Adult: As per NTEP India guidelines for Intensive Phase: For patients weighing 25-39 kg: 2 tablets daily (Rifampicin 300mg + INH 150mg). For patients weighing 40-54 kg: 3 tablets daily (Rifampicin 450mg + INH 225mg). For patients weighing 55-70 kg: 4 tablets daily (Rifampicin 600mg + INH 300mg). Doses are typically administered as a single daily dose.
Note: Take on an empty stomach, at least 1 hour before or 2 hours after meals, with a full glass of water to maximize absorption. If gastrointestinal upset occurs, can be taken with a small amount of low-fat food, acknowledging reduced Rifampicin bioavailability. Administer once daily, preferably in the morning. Pyridoxine (10-25 mg daily) should be co-administered to prevent neuropathy. Avoid antacids containing aluminum salts within 2 hours of dose.
The combination provides synergistic bactericidal activity against actively dividing Mycobacterium tuberculosis. Rifampicin binds to the beta subunit of bacterial DNA-dependent RNA polymerase, blocking RNA synthesis. Isoniazid, a prodrug, is activated by the bacterial catalase-peroxidase enzyme (KatG), forming an active species that inhibits the enzyme enoyl-acyl carrier protein reductase (InhA), disrupting the synthesis of mycolic acids, essential components of the mycobacterial cell wall.
Pregnancy: Pregnancy Category C (US FDA). Considered generally safe and recommended for treatment of active TB in pregnancy by WHO and NTEP. The benefit of treating active TB far outweighs the risk. Pyridoxine supplementation (25 mg/day) is essential. Monitor LFTs.
Driving: Generally safe. However, patients should be cautioned about potential dizziness, visual disturbances, or fatigue, especially during initial therapy.
| Ketoconazole, Itraconazole, Voriconazole | Rifampicin drastically reduces azole levels, leading to therapeutic failure. | Major |
| Oral Contraceptives, Hormonal Replacement Therapy | Rifampicin induces metabolism, causing contraceptive failure and breakthrough bleeding. | Major |
| Warfarin, Acenocoumarol | Rifampicin reduces anticoagulant effect; increased INR monitoring required. | Major |
| Antiretroviral Protease Inhibitors (e.g., Ritonavir, Lopinavir) & NNRTIs (e.g., Nevirapine, Efavirenz) | Complex bidirectional interactions; Rifampicin reduces levels of most PIs. Co-administration requires expert HIV/TB management and dose adjustments. | Major |
| Oral Hypoglycemics (e.g., Glimepiride, Glyburide) | Rifampicin may reduce their efficacy, worsening glycemic control. | Moderate |
| Digoxin | Rifampicin reduces serum digoxin levels. | Moderate |
| Theophylline | Rifampicin increases its clearance, reducing efficacy. | Moderate |
| Phenytoin, Valproate | Rifampicin reduces levels; INH may inhibit phenytoin metabolism, increasing levels. Monitor drug levels. | Major |
| Corticosteroids (e.g., Prednisolone) | Rifampicin increases metabolism, reducing therapeutic effect. | Moderate |
| Acetaminophen (Paracetamol) | INH may potentiate hepatotoxicity, especially in overdose. | Moderate |
Same composition (Rifampicin (150mg) + Isoniazid (75mg)), different brands: