Dosing and Administration of Anti-Tuberculosis Drugs in CKD Patients
For patients with chronic kidney disease (CKD), anti-tuberculosis medications require specific dosage adjustments based on renal function, with some drugs requiring frequency changes rather than dose reductions to maintain efficacy while preventing toxicity. 1
First-Line Anti-TB Drugs in CKD
Drugs Not Requiring Dose Adjustment
- Isoniazid (INH) and rifampin (RIF) are primarily metabolized by the liver and can be given at standard doses in renal insufficiency 1
- Standard dosing: INH 300 mg once daily or 900 mg three times weekly; RIF 600 mg once daily or 600 mg three times weekly 1
Drugs Requiring Dose Adjustment
- Pyrazinamide (PZA) is metabolized by the liver but its metabolites (pyrazinoic acid and 5-hydroxy-pyrazinoic acid) accumulate in renal insufficiency 1
- Ethambutol (EMB) is approximately 80% cleared by the kidneys and may accumulate in patients with renal insufficiency 1
- For patients with creatinine clearance <30 mL/min or on hemodialysis:
Second-Line Anti-TB Drugs in CKD
- Fluoroquinolones: Levofloxacin requires adjustment (750-1000 mg three times weekly), while moxifloxacin (400 mg daily) does not 1, 2
- Injectable agents (streptomycin, kanamycin, amikacin, capreomycin): All require adjustment to 15 mg/kg/dose 2-3 times weekly 1
- Cycloserine: 250 mg once daily or 500 mg three times weekly 1
- Ethionamide: No adjustment needed (250-500 mg/dose daily) 1
- Para-aminosalicylic acid: No adjustment needed (4 g/dose twice daily) 1
Hemodialysis Considerations
- Administer all anti-TB medications after hemodialysis sessions to prevent premature drug clearance 1
- PZA and its metabolites are cleared significantly by hemodialysis 1
- INH and EMB are cleared to some degree by hemodialysis 1
- RIF is not cleared by hemodialysis due to its high molecular weight, wide tissue distribution, high protein binding, and rapid hepatic metabolism 1
Monitoring Recommendations
- Measure creatinine clearance before starting treatment, especially when using drugs cleared by the kidneys 1
- For patients with borderline renal function, consider 24-hour urine collection to accurately define the degree of renal insufficiency 1
- Monitor serum drug concentrations to ensure adequate absorption without excessive accumulation 1
- For patients with creatinine clearance between 30-50 mL/min, standard doses can be used, but consider measuring serum concentrations at 2 and 6 hours after administration to optimize dosing 1
Special Considerations
- Patients with CKD are at increased risk of developing tuberculosis due to immunosuppression 3, 4
- CKD patients often take other medications that may interact with anti-TB drugs 1
- Adverse events are more common in severe CKD, even with appropriate dose adjustments 5, 6
- Drug-induced hepatitis and cutaneous reactions are significant risk factors for regimen changes in CKD patients 5
Peritoneal Dialysis
- Begin with doses recommended for hemodialysis patients and verify adequacy using serum concentration monitoring 1
- Limited data exists for peritoneal dialysis patients, requiring closer monitoring 1
Pitfalls to Avoid
- Decreasing the dose rather than extending the interval may lead to suboptimal peak serum concentrations and reduced efficacy 1
- Administering drugs before hemodialysis can result in premature clearance, especially for PZA 1
- Failing to monitor for unusual adverse effects, which may be more severe in kidney patients due to decreased renal elimination 6
- Not adjusting doses appropriately can lead to drug accumulation and toxicity, particularly with EMB and aminoglycosides 1
By following these guidelines for anti-TB drug dosing in CKD patients, clinicians can optimize treatment efficacy while minimizing adverse effects and improving outcomes.