1. Clinical Overview
A fixed-dose combination (FDC) of three first-line anti-tubercular drugs used primarily in the intensive phase of treatment for drug-susceptible pulmonary and extrapulmonary tuberculosis. This specific low-dose combination is often used in pediatric formulations or for specific weight-band dosing in adults under the Revised National Tuberculosis Control Programme (RNTCP), now known as the National Tuberculosis Elimination Programme (NTEP) in India. It is a cornerstone of Directly Observed Treatment, Short-course (DOTS) strategy.
| Onset | Duration | Bioavailability |
|---|---|---|
| Isoniazid: 1-2 hours; Rifampicin: 2-4 hours; Pyrazinamide: 1-2 hours. | Isoniazid: 24 hours; Rifampicin: 24 hours; Pyrazinamide: 24 hours. | Isoniazid: ~90% (oral); Pyrazinamide: >90% (oral); Rifampicin: ~90% on empty stomach, significantly reduced with food. |
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 treatment of newly diagnosed, drug-susceptible pulmonary tuberculosis.
- Intensive phase treatment of extrapulmonary tuberculosis (e.g., lymph node, pleural, genitourinary).
- Treatment of tuberculosis as per the National Tuberculosis Elimination Programme (NTEP) guidelines for specific weight bands.
4. Dosage & Administration
Adult Dosage: Dosing is weight-based as per NTEP guidelines. This specific FDC (50+300+100mg) is typically used for patients in the 16-25kg weight band (e.g., 2 tablets daily). For standard adult dosing (e.g., 30-39kg: 3 tablets; 40-54kg: 4 tablets; 55-69kg: 5 tablets), taken once daily on an empty stomach.
Administration: Take all tablets as a single daily dose, preferably 1 hour before or 2 hours after a meal (empty stomach) with water to maximize Rifampicin absorption. Do not break or crush unless specified (some pediatric formulations are dispersible). Adhere strictly to the prescribed duration (usually 2 months intensive phase).
5. Side Effects
Common side effects may include:
- Orange/red discoloration of urine, sweat, tears, and other body fluids (Rifampicin).
- Nausea, vomiting, abdominal discomfort.
- Skin rash, itching.
- Hyperuricemia (asymptomatic) due to Pyrazinamide.
- Transient asymptomatic elevation of liver enzymes.
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Ketoconazole, Itraconazole, Fluconazole | Rifampicin decreases azole levels, reducing antifungal efficacy. | Major |
| Warfarin, Acenocoumarol | Rifampicin increases metabolism, reducing anticoagulant effect. Dose adjustment and frequent INR monitoring needed. | Major |
| Oral Contraceptives, Levonorgestrel | Rifampicin reduces efficacy, leading to contraceptive failure. Alternative non-hormonal methods advised. | Major |
| Antiretroviral Drugs (e.g., Protease Inhibitors, NNRTIs) | Complex bidirectional interactions. Rifampicin significantly lowers levels of many ARVs. Requires expert HIV/TB co-management and regimen adjustment. | Major |
| Phenytoin, Carbamazepine | Rifampicin increases metabolism, reducing anticonvulsant levels. Isoniazid can inhibit metabolism, increasing levels. Monitor levels closely. | Major |
| Prednisolone, Dexamethasone | Rifampicin increases metabolism, reducing corticosteroid efficacy. | Moderate |
| Antacids (Aluminum hydroxide) | May reduce absorption of Isoniazid. Administer at least 2 hours apart. | Moderate |
| Acetaminophen (Paracetamol) | Increased risk of hepatotoxicity, especially with Isoniazid. | Moderate |
| Theophylline | Rifampicin decreases theophylline levels. | Moderate |
| Cyclosporine, Tacrolimus | Rifampicin drastically reduces levels, risking transplant rejection. | Major |
7. Patient Counselling
- DO take the medicine at the same time every day, on an empty stomach (1 hr before or 2 hrs after food).
- DO complete the full course of treatment, even if you feel better, to prevent relapse and drug resistance.
- DO inform all your doctors (including dentist) that you are on anti-TB treatment.
- DO take Pyridoxine (Vitamin B6) supplement if prescribed to prevent neuropathy.
- DON'T consume alcohol in any form during and for some time after treatment.
- DON'T miss doses. If you miss a dose, take it as soon as you remember, but if it's almost time for the next dose, skip the missed dose. Do NOT double the dose.
- DON'T take any other medicines (including OTC, herbal, Ayurvedic) without consulting your doctor.
8. Toxicology & Storage
Overdose: Nausea, vomiting, abdominal pain, lethargy, slurred speech, dizziness, visual disturbances. Severe overdose: Liver enlargement with tenderness, jaundice (hepatotoxicity), metabolic acidosis, seizures (Isoniazid-induced), oliguria, acute renal failure.
Storage: Store below 30°C, in a cool, dry place, protected from light and moisture. Keep the container tightly closed. Keep out of reach of children. Do not use after the expiry date printed on the pack.