1. Clinical Overview
Sodium aminosalicylate (Sodium PAS) is a bacteriostatic antitubercular agent, specifically a second-line drug used in the treatment of multidrug-resistant tuberculosis (MDR-TB). It is a sodium salt of para-aminosalicylic acid. Its use has declined with the advent of more potent and better-tolerated drugs like ethambutol, but it remains a critical component in salvage regimens for drug-resistant TB, especially in the Indian context where MDR-TB burden is high. It acts by inhibiting folic acid synthesis in Mycobacterium tuberculosis.
| Onset | Duration | Bioavailability |
|---|---|---|
| Therapeutic effects are observed after several weeks of continuous therapy as part of a combination regimen. | Approximately 24 hours, necessitating multiple daily doses. | Well absorbed from the gastrointestinal tract, estimated at 80-90%. |
2. Mechanism of Action
Sodium aminosalicylate is a structural analog of para-aminobenzoic acid (PABA). It competitively inhibits the enzyme dihydropteroate synthase (DHPS), which is involved in the bacterial folate biosynthesis pathway. This inhibition depletes the pool of dihydrofolic acid, a precursor for tetrahydrofolate, which is an essential cofactor in the synthesis of thymidine, purines, and certain amino acids. This ultimately inhibits bacterial DNA replication and cell growth.
3. Indications & Uses
- Multidrug-Resistant Tuberculosis (MDR-TB) as part of a WHO-recommended longer regimen
- Extensively Drug-Resistant Tuberculosis (XDR-TB) in combination regimens
- Intolerance or resistance to first-line anti-TB drugs (isoniazid, rifampicin)
4. Dosage & Administration
Adult Dosage: 8-12 grams per day, administered in 2-3 divided doses (e.g., 4g every 8 hours or 6g every 12 hours). The 1000mg tablet formulation would require 8-12 tablets daily.
Administration: Take with or immediately after food to minimize gastric irritation. Tablets should be swallowed whole with a full glass of water. Do not crush or chew. Doses should be evenly spaced. To improve tolerability, the total daily dose can be initiated at a lower level and gradually increased over 1-2 weeks.
5. Side Effects
Common side effects may include:
- Nausea, vomiting, epigastric discomfort
- Diarrhea
- Anorexia, abdominal pain
- Skin rash, pruritus
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Rifampicin | May decrease serum levels of Sodium PAS due to increased hepatic metabolism. Clinical significance uncertain but may reduce PAS efficacy. | Moderate |
| Isoniazid | PAS may increase isoniazid levels by competing for acetylation pathways, potentially increasing isoniazid toxicity (neuropathy, hepatitis). | Moderate |
| Digoxin | PAS may reduce the absorption of digoxin, potentially decreasing its efficacy. Administer digoxin at least 2 hours before PAS. | Moderate |
| Vitamin B12 (Cyanocobalamin) | PAS can impair the absorption of vitamin B12, potentially leading to megaloblastic anemia with long-term use. | Moderate |
| Methotrexate | Increased risk of hematological toxicity due to combined antifolate effects. | Major |
| Phenytoin | PAS may increase phenytoin levels, leading to toxicity (nystagmus, ataxia). Monitor phenytoin levels. | Moderate |
| Warfarin | May potentiate the anticoagulant effect by protein binding displacement and antifolate effects. Monitor INR closely. | Major |
| Probenecid | May increase serum levels of PAS by reducing renal tubular secretion. | Moderate |
7. Patient Counselling
- DO take this medicine exactly as prescribed, at evenly spaced intervals.
- DO take it with food or milk to reduce stomach upset.
- DO drink plenty of fluids (2-3 liters per day) to prevent kidney problems and crystalluria.
- DO complete the full course of therapy, which may last 18-24 months for MDR-TB.
- DO NOT skip doses, as this can lead to treatment failure and further drug resistance.
- DO NOT crush or chew the tablets; swallow whole with water.
- DO NOT take antacids or digoxin within 2 hours of taking this medicine.
8. Toxicology & Storage
Overdose: Acute overdose primarily manifests as severe nausea, vomiting, diarrhea, abdominal pain leading to dehydration and electrolyte imbalance (hypokalemia, metabolic acidosis). Crystalluria, hematuria, and acute kidney injury may occur. In severe cases, CNS effects like dizziness, confusion, and metabolic acidosis can be seen.
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.