1. Clinical Overview
Isoniazid (INH) is a first-line, bactericidal antitubercular agent, considered a cornerstone of tuberculosis (TB) treatment and prevention in India. It is a prodrug activated by the bacterial catalase-peroxidase enzyme (KatG), leading to inhibition of mycolic acid synthesis, essential for the mycobacterial cell wall. It is highly effective against actively dividing Mycobacterium tuberculosis organisms and is a key component of the Directly Observed Treatment, Short-course (DOTS) strategy.
| Onset | Duration | Bioavailability |
|---|---|---|
| Peak plasma concentration is reached within 1-2 hours post oral administration. | Its bactericidal effect is concentration-dependent and persists due to its mechanism of action on cell wall synthesis. Dosing is typically once daily. | Approximately 90% following oral administration; absorption is reduced by food. |
2. Mechanism of Action
Isoniazid is a prodrug activated by the mycobacterial catalase-peroxidase enzyme (KatG). The activated form forms a covalent adduct with NAD+ and NADP+, which then potently inhibits the enoyl-acyl carrier protein reductase (InhA) enzyme. This inhibition disrupts the synthesis of mycolic acids, which are long-chain fatty acids critical for the formation and integrity of the mycobacterial cell wall.
3. Indications & Uses
- Active Pulmonary Tuberculosis (as part of combination therapy)
- Active Extrapulmonary Tuberculosis (e.g., meningeal, miliary, skeletal)
- Latent Tuberculosis Infection (LTBI) treatment and prevention
4. Dosage & Administration
Adult Dosage: Active TB: 5 mg/kg (usually 300 mg) once daily or 15 mg/kg (max 900 mg) 2-3 times per week under DOTS. LTBI: 5 mg/kg (max 300 mg) once daily for 6-9 months, or 900 mg twice weekly for 3 months.
Administration: 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 food, acknowledging reduced absorption. Pyridoxine (10-25 mg daily) should be co-administered. For LTBI, adherence is critical; use pill boxes or reminders.
5. Side Effects
Common side effects may include:
- Peripheral neuropathy (numbness, tingling in hands/feet)
- Asymptomatic elevation of liver transaminases (up to 20% of patients)
- Nausea, vomiting, epigastric discomfort
- Rash
- Pyridoxine deficiency
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Rifampicin | Increases risk of hepatotoxicity. Also induces INH metabolism, potentially lowering levels. | Major |
| Pyrazinamide | Synergistic hepatotoxicity risk. | Major |
| Phenytoin / Carbamazepine | INH inhibits their metabolism, leading to increased levels and toxicity (ataxia, nystagmus). | Major |
| Warfarin | INH may potentiate anticoagulant effect; monitor INR closely. | Moderate |
| Ketoconazole / Itraconazole | INH may decrease their plasma levels via CYP induction. | Moderate |
| Antacids (Aluminum-containing) | May decrease INH absorption. Separate administration by at least 2 hours. | Moderate |
| Acetaminophen (Paracetamol) | Increased risk of hepatotoxicity, especially in overdose settings. | Moderate |
| Disulfiram | Increased risk of neuropsychiatric reactions. | Moderate |
| Diazepam, Triazolam | INH may inhibit their metabolism, increasing sedation. | Moderate |
7. Patient Counselling
- DO take the medicine exactly as prescribed, at the same time each day.
- DO take pyridoxine (Vitamin B6) daily as advised by your doctor.
- DO take on an empty stomach for best effect.
- DO report any yellowing of eyes/skin, dark urine, loss of appetite, unexplained nausea/vomiting, or abdominal pain IMMEDIATELY.
- DO complete the full course of treatment, even if you feel better.
- DONT consume ANY alcohol during treatment and for some time after.
- DONT stop the medicine without consulting your doctor.
- DONT take with antacids without a 2-hour gap.
8. Toxicology & Storage
Overdose: Occurs within 30 min to 3 hours. Symptoms include: nausea, vomiting, slurred speech, dizziness, blurred vision, visual hallucinations, seizures (often refractory), metabolic acidosis (elevated anion gap), hyperglycemia, coma, and respiratory distress. Acute hepatic necrosis may follow within 24-48 hours.
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.