A fixed-dose combination (FDC) of two first-line bactericidal antitubercular drugs used primarily in the intensive phase of treatment for drug-sensitive pulmonary and extrapulmonary tuberculosis. Isoniazid is a potent bactericidal agent against actively dividing Mycobacterium tuberculosis, while Ethambutol is a bacteriostatic agent that inhibits cell wall synthesis. This combination is a cornerstone of the Revised National Tuberculosis Control Programme (RNTCP), now known as the National Tuberculosis Elimination Programme (NTEP), in India. It is used to prevent the emergence of drug resistance and to simplify therapy.
Adult: One tablet (Isoniazid 300mg + Ethambutol 800mg) once daily. Weight-based dosing for Ethambutol: 15-20 mg/kg/day. The 800mg dose is appropriate for patients weighing approximately 40-55 kg. For patients >55 kg, Ethambutol dose may need adjustment (often given as a separate tablet).
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 GI upset occurs, may be taken with a light, low-fat meal. Administer once daily, preferably in the morning. Pyridoxine (10-25 mg daily) should be co-administered, especially in high-risk patients (malnourished, diabetic, alcoholic, HIV+, pregnant, breastfeeding, renal failure).
Isoniazid is a prodrug activated by the bacterial catalase-peroxidase enzyme (KatG). The activated form inhibits the synthesis of mycolic acids, which are essential components of the mycobacterial cell wall. Ethambutol inhibits the enzyme arabinosyl transferase (embCAB operon), which is involved in the polymerization of arabinogalactan, another critical cell wall component. Together, they disrupt cell wall integrity, leading to bacterial cell death (Isoniazid) and inhibition of growth (Ethambutol).
Pregnancy: Pregnancy Category C (US FDA). Both drugs cross the placenta. Use only if clearly needed. Isoniazid is considered relatively safe with Pyridoxine supplementation. Ethambutol is also considered safe. Untreated TB poses a greater risk to the fetus. Close monitoring for hepatotoxicity is essential.
Driving: Caution advised. May cause dizziness, vertigo, and visual disturbances (blurred vision from Ethambutol). Patients should not drive or operate machinery until their individual response is known, especially if visual symptoms occur.
| Rifampicin | Increases hepatic metabolism of Isoniazid, potentially increasing hepatotoxic metabolites. Synergistic antitubercular effect. | Major |
| Pyrazinamide | Additive hepatotoxicity risk. Used together in standard HRZE regimen. | Major |
| Antacids (Aluminum hydroxide) | Decrease absorption of Ethambutol. Separate administration by at least 4 hours. | Moderate |
| Phenytoin, Carbamazepine | Isoniazid inhibits their metabolism, increasing serum levels and risk of toxicity (ataxia, nystagmus, drowsiness). | Major |
| Warfarin | Isoniazid may potentiate anticoagulant effect. Monitor INR closely. | Major |
| Ketoconazole, Itraconazole | Isoniazid may reduce their plasma concentrations. | Moderate |
| Alcohol | Increases risk of Isoniazid-induced hepatitis and CNS effects. Disulfiram-like reaction possible. | Major |
| Corticosteroids | May decrease Isoniazid efficacy by increasing renal excretion. | Moderate |
| Cycloserine | Increased risk of CNS toxicity (dizziness, seizures) with Isoniazid. | Moderate |
Same composition (Isoniazid (300mg) + Ethambutol (800mg)), different brands: