Which anti-tubercular (anti-tuberculosis) drugs require modification in patients with impaired renal function?

Anti-Tubercular Drugs Requiring Modification in Renal Dysfunction

In patients with renal dysfunction, the following anti-tubercular drugs require dosage modification: pyrazinamide, ethambutol, streptomycin, amikacin, kanamycin, capreomycin, cycloserine, and levofloxacin. 1 The primary approach is to maintain the same dose but increase the dosing interval rather than reducing the dose.

Drugs That Require Modification

Injectable Aminoglycosides and Polypeptides

These drugs require the most significant adjustments as they are primarily eliminated by the kidneys:

• Streptomycin, Amikacin, Kanamycin, Capreomycin
  • Normal dosing: 15 mg/kg/day (max 1g/day)
  • In renal dysfunction: Maintain dose at 12-15 mg/kg but reduce frequency to 2-3 times weekly 1
  • These drugs should be given after hemodialysis to avoid premature removal 1
  • Serum drug concentrations should be monitored to avoid toxicity 1

Oral First-Line Drugs

• Pyrazinamide (PZA)

  • Although metabolized by the liver, its metabolites accumulate in renal insufficiency 1
  • In renal dysfunction: 25-35 mg/kg per dose three times weekly (not daily) 1

• Ethambutol (EMB)

  • Approximately 80% cleared by kidneys 1
  • In renal dysfunction: 15-25 mg/kg per dose three times weekly (not daily) 1

• Levofloxacin

  • In renal dysfunction: 750-1,000 mg per dose three times weekly (not daily) 1

• Cycloserine

  • In renal dysfunction: 250 mg once daily, or 500 mg/dose three times weekly 1

Drugs That Do Not Require Modification

• Isoniazid (INH)

  • Metabolized by the liver; no dosage adjustment needed 1
  • Standard dose: 300 mg once daily or 900 mg three times weekly 1

• Rifampin (RIF)

  • Metabolized by the liver; no dosage adjustment needed 1
  • Standard dose: 600 mg once daily or 600 mg three times weekly 1

• Ethionamide

  • Not cleared by kidneys; no dosage adjustment needed 1
  • Standard dose: 250-500 mg/dose daily 1

• Para-aminosalicylic acid (PAS)

  • Only modestly cleared by hemodialysis 1
  • Standard dose: 4 g/dose, twice daily 1

Monitoring Recommendations

1. Baseline Assessment

   • Renal function tests before starting treatment
   • Identify risk factors: age >59 years, diabetes, hypertension, pre-existing renal disease 2

2. Ongoing Monitoring

   • Monthly renal function tests for all patients
   • More frequent monitoring (every 1-2 weeks) for high-risk patients 2
   • For aminoglycosides: monthly auditory and vestibular function tests 1, 2

3. Therapeutic Drug Monitoring

   • Essential for amikacin therapy
   • Target peak levels: 25-35 μg/mL
   • Target trough levels: <5-10 μg/mL 2

Important Clinical Considerations

1. Administration Timing

   • All anti-TB drugs should be administered after hemodialysis to avoid drug removal and facilitate directly observed therapy 1

2. Concentration-Dependent Bactericidal Effect

   • For aminoglycosides, maintaining the dose is critical for efficacy while extending the interval between doses helps reduce toxicity 1

3. Age-Related Adjustments

   • For patients >59 years old receiving aminoglycosides, reduce dose to 10 mg/kg/day (max 750 mg) even with normal renal function 1

4. Pregnancy Considerations

   • Aminoglycosides are contraindicated in pregnancy due to risk of fetal nephrotoxicity and congenital hearing loss 1, 2

Approach to Dosing in Renal Dysfunction

1. Estimate or measure creatinine clearance
2. For patients with creatinine clearance <30 ml/min or on hemodialysis, follow the dosing recommendations in Table 15 1
3. For patients with creatinine clearance between 30-80 ml/min, use standard doses but consider therapeutic drug monitoring 1
4. Administer all drugs after hemodialysis sessions

This approach ensures effective tuberculosis treatment while minimizing drug toxicity in patients with renal dysfunction.