Anti-Tuberculosis Treatment Plan for 71 kg Male with Creatinine 2.8 mg/dL
Initial Assessment
This patient requires dose adjustment for pyrazinamide and ethambutol to three-times-weekly dosing, while isoniazid and rifampin can be given at standard doses. 1
First, calculate creatinine clearance to confirm the degree of renal impairment. With a creatinine of 2.8 mg/dL, this patient likely has a creatinine clearance <30 mL/min, placing him in the category requiring modified dosing. 1 If borderline, obtain a 24-hour urine collection for more accurate assessment before making regimen changes. 1
Recommended Treatment Regimen
Intensive Phase (First 2 Months)
Isoniazid (INH):
- 300 mg once daily (no dose adjustment needed) 1
- Metabolized by liver, safe in renal insufficiency 1
- Add pyridoxine 25-50 mg daily to prevent peripheral neuropathy 1
Rifampin (RIF):
- 600 mg once daily (no dose adjustment needed) 1
- Metabolized by liver, safe in renal insufficiency 1
- Note: Rifampin has been associated with acute interstitial nephritis in rare cases 2, 3, requiring close monitoring
Pyrazinamide (PZA):
- 25-35 mg/kg three times weekly (approximately 1750-2500 mg three times weekly for 71 kg) 1
- NOT daily dosing - frequency must be reduced 1
- Metabolites accumulate in renal insufficiency despite hepatic metabolism 1
Ethambutol (EMB):
- 20-25 mg/kg three times weekly (approximately 1400-1775 mg three times weekly for 71 kg) 1
- NOT daily dosing - frequency must be reduced 1
- 80% renally cleared, accumulates significantly in renal insufficiency 1
- Monitor for optic neuritis more carefully given renal impairment 1
Continuation Phase (Months 3-6)
Continue INH and RIF at same doses as above. 1
Critical Monitoring Requirements
Baseline Assessment:
- Measure creatinine clearance accurately 1
- Obtain baseline liver function tests 1
- Baseline visual acuity and color vision testing (for EMB) 1
- Assess for hemodialysis status 1
During Treatment:
- Serum drug concentration monitoring should be considered to ensure adequate absorption without excessive accumulation and avoid toxicity 1
- Measure concentrations at 2 and 6 hours after timed administration to optimize dosing 1
- Monthly clinical assessment for symptoms of hepatotoxicity (malaise, nausea, jaundice) 1
- Monthly visual acuity checks due to EMB use 1
- Monitor renal function closely as TB patients with chronic renal failure have worse clinical outcomes 1
Medication Administration Timing
If patient is on hemodialysis:
- Administer all medications after hemodialysis on dialysis days 1
- This facilitates directly observed therapy and prevents premature drug clearance 1
- PZA and metabolites are cleared significantly by dialysis; INH and EMB cleared to some degree; RIF not cleared 1
Key Pitfalls to Avoid
Do NOT use daily dosing for PZA and EMB - this is the most critical error to avoid. 1 Decreasing the dose lowers peak serum concentrations and compromises efficacy; instead, increase the interval between doses. 1
Avoid streptomycin or other aminoglycosides unless absolutely necessary, as they are exclusively renally excreted and carry high ototoxicity risk in renal failure. 1 If required, use 15 mg/kg two to three times weekly (not daily) with serum level monitoring. 1
Monitor for rifampin-induced acute interstitial nephritis, which is the leading cause of acute kidney injury during TB treatment. 2 If AKI develops (rising creatinine, eosinophilia, rash), stop all TB drugs immediately and consider short-term steroids. 2, 3 Levofloxacin 750-1000 mg three times weekly can replace rifampin if needed. 1, 2
Do not assume standard dosing is safe - patients with renal insufficiency are immunocompromised and require close monitoring throughout treatment. 1
Alternative Fluoroquinolone Dosing (if needed)
If rifampin must be avoided due to AKI: