1. Clinical Overview
A fixed-dose combination (FDC) of two first-line anti-tubercular drugs used primarily in the continuation phase of treatment for drug-sensitive pulmonary tuberculosis. Sodium aminosalicylate is a bacteriostatic agent that inhibits folate synthesis, while Isoniazid is a potent bactericidal agent that inhibits mycolic acid synthesis in the Mycobacterium tuberculosis cell wall. This combination is used to prevent the emergence of Isoniazid resistance and to provide synergistic anti-mycobacterial activity.
| Onset | Duration | Bioavailability |
|---|---|---|
| Isoniazid: Peak plasma concentration within 1-2 hours. Sodium aminosalicylate: Peak plasma concentration within 1.5-2 hours. | Approximately 24 hours for both components, supporting once-daily dosing. | Isoniazid: ~90% (oral). Sodium aminosalicylate: ~70-80% (oral). |
2. Mechanism of Action
The combination exerts a dual bactericidal and bacteriostatic effect on Mycobacterium tuberculosis. Isoniazid is a prodrug activated by the bacterial catalase-peroxidase enzyme (KatG). The activated form inhibits the enzyme enoyl-acyl carrier protein reductase (InhA), a key component of the fatty acid synthase II system, thereby disrupting the synthesis of mycolic acids, essential components of the mycobacterial cell wall. Sodium aminosalicylate is a structural analog of para-aminobenzoic acid (PABA). It competitively inhibits dihydropteroate synthase, blocking the incorporation of PABA into dihydrofolic acid, a precursor for folate synthesis. This inhibits bacterial DNA synthesis and replication.
3. Indications & Uses
- Continuation phase treatment of drug-sensitive pulmonary tuberculosis in adults and adolescents (as part of a multi-drug regimen)
4. Dosage & Administration
Adult Dosage: Typically 1 sachet/granules (containing Sodium aminosalicylate 1.145gm + Isoniazid 33.33mg) per 10 kg body weight per day, up to a maximum of 6 sachets daily. Exact dosing follows weight bands as per National TB Elimination Programme (NTEP) India guidelines. Example: 30-37 kg: 3 sachets/day; 38-54 kg: 4 sachets/day; 55-70 kg: 5 sachets/day; >70 kg: 6 sachets/day.
Administration: Administer granules/sachet contents orally, once daily, preferably on an empty stomach (1 hour before or 2 hours after food) to maximize absorption, especially of Sodium aminosalicylate. The granules should be mixed with water, milk, or fruit juice to form a suspension and consumed immediately. Do not chew the granules. Pyridoxine (Vitamin B6) supplementation (10-25 mg/day) is strongly recommended to prevent Isoniazid-induced peripheral neuropathy.
5. Side Effects
Common side effects may include:
- Nausea, vomiting, epigastric discomfort
- Diarrhea
- Loss of appetite
- Headache
- Dizziness
- Peripheral neuropathy (tingling, numbness)
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Rifampicin | Increases risk of hepatotoxicity. Monitor LFTs closely. | Major |
| Pyrazinamide | Additive hepatotoxicity risk. | Major |
| Phenytoin/Carbamazepine | Isoniazid inhibits metabolism, increasing anticonvulsant levels and toxicity risk. | Major |
| Warfarin | Isoniazid may potentiate anticoagulant effect. Monitor INR. | Moderate |
| Antacids (Aluminum containing) | May decrease absorption of Sodium aminosalicylate. Separate administration by 2-3 hours. | Moderate |
| Corticosteroids | May decrease Isoniazid efficacy by increasing its metabolism. | Moderate |
| Disulfiram | Concurrent use may cause coordination difficulties and psychotic episodes. | Moderate |
| Tyramine-rich foods (with Isoniazid as MAO inhibitor) | Risk of hypertensive crisis (cheese, fermented foods). | Moderate |
7. Patient Counselling
- DO take the medicine exactly as prescribed, at the same time each day.
- DO take it on an empty stomach (1 hr before or 2 hrs after meals).
- DO take the prescribed Pyridoxine (Vitamin B6) supplement daily.
- DO report any symptoms of liver problems (yellow eyes/skin, dark urine, unusual tiredness, nausea for >1 day) immediately.
- DO complete the full course of treatment, even if you feel better.
- DON'T consume alcohol in any form during treatment.
- DON'T miss doses. If you miss one, take it as soon as you remember, but skip if it's almost time for the next dose. Do not double dose.
- DON'T take antacids within 2-3 hours of this medicine.
8. Toxicology & Storage
Overdose: Isoniazid overdose (≥1.5g) is a medical emergency. Symptoms appear within 30 min to 3 hours: Severe nausea/vomiting, slurred speech, dizziness, visual disturbances, hallucinations, seizures (often refractory), metabolic acidosis (high anion gap), hyperglycemia, coma, and respiratory depression. Sodium aminosalicylate overdose: Severe GI distress (nausea, vomiting, diarrhea), electrolyte imbalance, crystalluria, possible renal damage, and metabolic acidosis.
Storage: Store in a cool, dry place, protected from light and moisture. Keep the sachets/granules in their original packaging until use. Keep out of reach of children. Do not use after the expiry date printed on the pack. Storage temperature: Below 30°C.