Why are sodium aminosalicylate granules given with antitubercular (anti-tuberculosis) medication?

Sodium Aminosalicylate Granules in Antitubercular Therapy

Sodium aminosalicylate (PAS) granules are given with antitubercular medication specifically for the treatment of drug-resistant tuberculosis caused by organisms that are susceptible to the drug. 1 This second-line agent plays a critical role in multidrug-resistant tuberculosis (MDR-TB) treatment regimens when first-line agents cannot be used due to resistance or intolerance.

Role in Tuberculosis Treatment

PAS is not a first-line agent for standard tuberculosis treatment. It is specifically reserved for:

• Treatment of drug-resistant tuberculosis
• Cases where first-line agents cannot be used due to adverse effects
• As part of a comprehensive regimen for MDR-TB

Dosing and Administration

• Adults: 8-12 g/day in two or three doses
  • For PAS granules, 4 g three times daily is the usual dosage, though 4 g twice daily has been shown to be adequate 1
• Children: 200-300 mg/kg per day in two to four divided doses 1

The only available formulation in the United States is granules in 4-g packets (Paser Granules®). While previously thought to require administration with acidic food, more recent data suggest this is not necessary 1.

Mechanism of Action and Resistance Prevention

PAS works as part of a multi-drug regimen to prevent the development of resistance to other antitubercular medications. When combined with other active agents, it helps reduce the bacterial population and decreases the probability of selecting drug-resistant mutants 2.

Adverse Effects

PAS has several notable adverse effects that require monitoring:

1. Gastrointestinal distress: Most common side effect (11% of patients in one large study) 1

   • Less common with lower doses (8 g daily)
   • Less common with the granular formulation

2. Hepatotoxicity: In a review of 7,492 patients, 0.5% developed hepatitis, with 0.3% attributed at least partly to PAS 1

3. Hypothyroidism: Common with prolonged administration or concomitant use of ethionamide

   • May require thyroid hormone replacement
   • Thyroid function returns to normal after discontinuation 1

4. Malabsorption syndrome: Characterized by steatorrhea and low serum folate levels 1

5. Coagulopathy: Doubling of prothrombin time has been reported 1

Special Considerations

• Renal disease: Approximately 80% of PAS is excreted in the urine. It is contraindicated in severe renal insufficiency unless no alternative exists, due to accumulation of the acetylated form 1

• Hepatic disease: PAS clearance is not substantially altered in liver disease, but requires increased laboratory and clinical monitoring 1

• Pregnancy: No human studies available, but PAS has been used safely in pregnancy. Should only be used if no alternatives exist for pregnant women with MDR-TB 1

• CNS penetration: In inflamed meninges, PAS concentrations are 10-50% of serum levels, making it marginally effective for TB meningitis 1

Monitoring Requirements

• Hepatic enzymes and thyroid function should be measured at baseline
• With prolonged therapy (more than 3 months), thyroid function should be checked every 3 months 1

Clinical Pitfalls to Avoid

1. Inadequate monitoring: Failure to monitor thyroid function can lead to undetected hypothyroidism

2. Renal function: Using standard doses in patients with severe renal impairment can lead to toxicity

3. Gastrointestinal intolerance: Not addressing GI side effects may lead to poor adherence

4. Drug interactions: Potential interactions with other medications should be evaluated before starting therapy

5. Inappropriate use: Using PAS as a first-line agent when not indicated can expose patients to unnecessary side effects

By understanding the specific role of PAS in antitubercular therapy and managing its potential adverse effects appropriately, clinicians can optimize outcomes for patients with drug-resistant tuberculosis.