A fixed-dose combination (FDC) of two first-line bactericidal antitubercular drugs (Isoniazid and Rifampicin) with Pyridoxine (Vitamin B6) added to mitigate Isoniazid-induced peripheral neuropathy. This combination forms the cornerstone of the intensive phase of the standard 6-month regimen for drug-susceptible pulmonary and extrapulmonary tuberculosis, as per the Revised National Tuberculosis Control Programme (RNTCP), now known as the National Tuberculosis Elimination Programme (NTEP) in India. It is a critical component of the Directly Observed Treatment, Short-course (DOTS) strategy.
Adult: One tablet (Isoniazid 300mg + Rifampicin 450mg + Pyridoxine 10mg) once daily, taken on an empty stomach (at least 1 hour before or 2 hours after food), preferably in the morning. Weight-based dosing as per NTEP guidelines: For patients ≥25 kg, this FDC is standard. For patients 25-39 kg, a different FDC (Isoniazid 225mg + Rifampicin 300mg) is used.
Note: Swallow whole with a full glass of water. MUST be taken on an empty stomach for optimal Rifampicin absorption. If gastrointestinal upset occurs, consult a doctor; taking with a small amount of low-fat food may be considered but is suboptimal. Avoid antacids (especially aluminum-containing) within 2 hours of dose. Do not crush or chew. Adherence to the prescribed schedule is paramount.
Isoniazid is a prodrug activated by the bacterial catalase-peroxidase enzyme (KatG). It inhibits the synthesis of mycolic acids, essential components of the mycobacterial cell wall, leading to bactericidal activity against actively dividing bacilli. Rifampicin binds to the beta subunit of bacterial DNA-dependent RNA polymerase, inhibiting RNA synthesis and causing bactericidal activity against both intracellular and extracellular bacilli. Pyridoxine does not have antitubercular activity; it serves as a cofactor and replenishes depleted stores to prevent neuropathy caused by Isoniazid's interference with pyridoxine metabolism.
Pregnancy: Pregnancy Category C (US FDA). Both drugs cross the placenta. Use is recommended for active TB in pregnancy as benefits outweigh risks. Pyridoxine is safe and recommended at higher doses (25 mg/day) to protect the fetus. Close monitoring for hepatotoxicity is essential. Newborns of mothers on Isoniazid should receive Pyridoxine supplementation.
Driving: Generally safe. However, patients should be cautioned about potential dizziness, visual disturbances (rare optic neuritis), or fatigue, especially during initial therapy.
| Ketoconazole, Itraconazole, Fluconazole (oral) | Rifampicin decreases azole levels, reducing antifungal efficacy. | Major |
| Warfarin, Acenocoumarol | Rifampicin increases metabolism, drastically reducing anticoagulant effect. Requires INR monitoring and dose increase. | Major |
| Oral Contraceptives (estrogen-based) | Rifampicin reduces contraceptive levels, leading to contraceptive failure. Alternative non-hormonal methods are essential. | Major |
| Antiretroviral Protease Inhibitors (e.g., Atazanavir, Lopinavir) & NNRTIs (e.g., Nevirapine) | Complex bidirectional interactions. Rifampicin significantly lowers PI levels. Co-administration is generally contraindicated; requires expert HIV-TB co-management and regimen adjustment (e.g., using Rifabutin). | Contraindicated/Major |
| Phenytoin, Carbamazepine, Valproate | Rifampicin increases metabolism, reducing anticonvulsant levels. Isoniazid can inhibit metabolism of Phenytoin, increasing its levels. Close monitoring of drug levels is needed. | Major |
| Prednisolone, Dexamethasone | Rifampicin increases steroid metabolism, reducing therapeutic effect. | Moderate |
| Digoxin | Rifampicin decreases Digoxin levels (P-glycoprotein induction). | Moderate |
| Theophylline | Rifampicin decreases Theophylline levels. | Moderate |
| Cyclosporine, Tacrolimus | Rifampicin decreases immunosuppressant levels, risking organ transplant rejection. | Major |
| Acetaminophen (Paracetamol) | Increased risk of hepatotoxicity, especially in overdose. Chronic use should be avoided. | Moderate |
| Antacids (Aluminum hydroxide) | Reduce absorption of Isoniazid. Administer at least 2 hours apart. | Moderate |
| Tyramine-rich foods (with Isoniazid) | Isoniazid is a weak MAO inhibitor; can cause mild hypertensive reactions. | Minor |
Same composition (Isoniazid (300mg) + Vitamin B6 (Pyridoxine) (10mg) + Rifampicin (450mg)), different brands: