1. Clinical Overview
A first-line, fixed-dose combination (FDC) anti-tubercular therapy (ATT) used in the intensive phase of treatment for drug-susceptible pulmonary and extrapulmonary tuberculosis. This specific strength is a standard 4-drug FDC used in the initial 2-month intensive phase under the Revised National Tuberculosis Control Programme (RNTCP), now known as the National Tuberculosis Elimination Programme (NTEP) in India. It is designed to improve adherence, prevent monotherapy, and reduce the risk of drug resistance.
| Onset | Duration | Bioavailability |
|---|---|---|
| Isoniazid: 1-2 hours; Rifampicin: 2-4 hours; Ethambutol: 2-4 hours; Pyrazinamide: 2-4 hours. | Isoniazid: 24 hours; Rifampicin: 24 hours; Ethambutol: 24 hours; Pyrazinamide: 24 hours. | Isoniazid: ~90% (oral); Rifampicin: ~90-95% (oral, reduced by food); Ethambutol: ~75-80% (oral); Pyrazinamide: >90% (oral). |
2. Mechanism of Action
Combination therapy targeting multiple, distinct biochemical pathways in Mycobacterium tuberculosis to achieve bactericidal and sterilizing effects, preventing the emergence of resistance.
3. Indications & Uses
- Intensive phase (first 2 months) of treatment for newly diagnosed, drug-susceptible pulmonary tuberculosis.
- Intensive phase (first 2 months) of treatment for extrapulmonary tuberculosis (e.g., lymph node, pleural, genitourinary, bone & joint, meningeal*). *For TB meningitis, Ethambutol is often replaced by Streptomycin.
4. Dosage & Administration
Adult Dosage: For patients weighing 30-39 kg: 2 tablets daily. For patients weighing 40-54 kg: 3 tablets daily. For patients weighing 55-70 kg: 4 tablets daily. As per NTEP guidelines, this FDC is used in the intensive phase. Dose is once daily, preferably in the morning on an empty stomach.
Administration: Take all tablets as a single daily dose, preferably in the morning, at least 1 hour before or 2 hours after food with a full glass of water. Do not break or crush tablets. Adhere strictly to the prescribed duration (usually 56 doses over 8 weeks). If a dose is missed, take it as soon as remembered, but if it's almost time for the next dose, skip the missed dose. Do not double the dose.
5. Side Effects
Common side effects may include:
- Orange/red discoloration of urine, sweat, tears, saliva (Rifampicin - harmless).
- Nausea, vomiting, abdominal discomfort.
- Skin rash, pruritus.
- Arthralgia, hyperuricemia (Pyrazinamide).
- Peripheral neuropathy (Isoniazid) - paresthesia, numbness.
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Ketoconazole, Itraconazole | Rifampicin reduces azole levels, causing therapeutic failure. | Major |
| Oral Contraceptives | Rifampicin reduces efficacy, leading to unintended pregnancy. | Major |
| Warfarin | Rifampicin reduces anticoagulant effect; increased dose needed. Monitor INR closely. | Major |
| Antiretroviral Protease Inhibitors (e.g., Saquinavir) | Rifampicin drastically reduces levels; contraindicated. | Contraindicated |
| Phenytoin | Rifampicin & Isoniazid alter phenytoin levels. Monitor levels. | Major |
| Pyridoxine (Vitamin B6) | Prevents Isoniazid-induced peripheral neuropathy. | Beneficial |
| Antacids (Aluminum hydroxide) | Reduce absorption of Ethambutol and Isoniazid. | Moderate |
| Acetaminophen (Paracetamol) | Increased risk of hepatotoxicity with Isoniazid. | Moderate |
7. Patient Counselling
- DO take the medicine at the same time every day, on an empty stomach.
- DO complete the full course of treatment, even if you feel better.
- DO take Pyridoxine (Vitamin B6) supplement if prescribed to prevent nerve problems.
- DO inform all your doctors and dentists you are on TB treatment.
- DO get regular check-ups and blood tests as advised.
- DON'T drink alcohol during treatment.
- DON'T miss doses. If you miss one, take it as soon as you remember, but never double the dose.
- DON'T take antacids within 2 hours of this medicine.
8. Toxicology & Storage
Overdose: Nausea, vomiting, abdominal pain, lethargy, slurred speech, dizziness, visual disturbances (blurring, color vision defects), headache, metabolic acidosis, seizures, coma, hepatotoxicity (jaundice, coagulopathy), acute renal failure.
Storage: Store below 30°C, in a cool, dry place, protected from light and moisture. Keep in the original blister pack until use. Keep out of reach of children. Do not use after the expiry date printed on the pack.