A fixed-dose combination (FDC) of two first-line bactericidal antitubercular drugs. Rifampicin is a rifamycin antibiotic, and Isoniazid is a synthetic isonicotinic acid hydrazide. This combination is a cornerstone of the Directly Observed Treatment, Short-course (DOTS) strategy for tuberculosis (TB) 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-susceptible pulmonary and extrapulmonary TB.
Adult: One tablet (Rifampicin 450mg + Isoniazid 300mg) daily, as per NTEP weight band: Typically for patients weighing 55-70 kg. For patients >70 kg, additional Rifampicin 150mg may be needed. Must be taken on an empty stomach.
Note: Take on an empty stomach, at least 1 hour before or 2 hours after a meal, with a full glass of water. Avoid antacids (especially aluminum-containing) within 2 hours. For patients experiencing GI upset, taking with a small, low-fat snack may be considered if supervised, though it reduces bioavailability. Adherence must be directly observed (DOTS).
Rifampicin inhibits DNA-dependent RNA polymerase in susceptible Mycobacterium tuberculosis, thereby suppressing RNA synthesis. Isoniazid is a prodrug activated by bacterial catalase-peroxidase (KatG), inhibiting the synthesis of mycolic acids, essential components of the mycobacterial cell wall. Their combination provides synergistic bactericidal activity against actively dividing intracellular and extracellular bacilli.
Pregnancy: Pregnancy Category C (US FDA). Both drugs cross the placenta. Use is recommended for active TB in pregnancy as benefits outweigh risks. However, the combination should be used under strict supervision. Pyridoxine supplementation (25-50 mg/day) is essential for the mother. Neonatal bleeding due to vitamin K deficiency (rifampicin effect) is a theoretical risk.
Driving: May cause dizziness, visual disturbances, or fatigue. Patients should not drive or operate machinery until they know how the medication affects them.
| Warfarin | Rifampicin induces metabolism, decreasing anticoagulant effect. INR monitoring crucial. | Major |
| Oral Contraceptives | Rifampicin induces metabolism, causing contraceptive failure. Alternative non-hormonal methods required. | Major |
| Antiretroviral Protease Inhibitors (e.g., Atazanavir, Darunavir) & NNRTIs (e.g., Nevirapine) | Rifampicin drastically reduces levels. Contraindicated or requires complex regimen adjustment. | Contraindicated/Major |
| Ketoconazole, Itraconazole | Rifampicin reduces azole levels; azoles may increase rifampicin toxicity. Avoid combination. | Major |
| Corticosteroids (e.g., Prednisolone) | Rifampicin increases metabolism, reducing therapeutic effect. | Moderate |
| Phenytoin, Carbamazepine | Mutual induction of metabolism; levels of both drugs become unpredictable. Monitor levels. | Major |
| Theophylline | Rifampicin increases clearance, reducing efficacy. | Moderate |
| Pyridoxine (Vitamin B6) | Prevents/treats Isoniazid-induced peripheral neuropathy. Often co-prescribed. | Beneficial |
| Acetaminophen (Paracetamol) | Increased risk of hepatotoxicity with Isoniazid. Use with caution. | Moderate |
| Antacids (Aluminum hydroxide) | Reduce absorption of Isoniazid. Administer at least 2 hours apart. | Moderate |
Same composition (Rifampicin (450mg) + Isoniazid (300mg)), different brands: