For a hemodialysis patient on the HRZE fixed‑dose combination for tuberculosis, should isoniazid and rifampicin be administered on non‑dialysis days?

HRZE FDC Administration in Hemodialysis Patients

Direct Answer

Yes, isoniazid (H) and rifampin (R) should be administered on non-dialysis days in hemodialysis patients receiving HRZE fixed-dose combination therapy, but the FDC formulation itself should NOT be used in dialysis patients—individual drug components must be given separately with modified dosing schedules. 1, 2

Critical Contraindication of FDC in Dialysis

Fixed-dose combination preparations (Rifamate® and Rifater®) are contraindicated in patients with renal insufficiency and end-stage renal disease. 2 The CDC explicitly states that FDCs should not be used in patients with renal insufficiency because:

• Pyrazinamide (Z) and ethambutol (E) require dosing interval adjustments that cannot be achieved with fixed combinations 1
• The fixed ratios are incompatible with the three-times-weekly dosing required for renally-cleared drugs 1

Correct Dosing Strategy for Dialysis Patients

Isoniazid and Rifampin (HR)

Administer on BOTH dialysis and non-dialysis days using one of these schedules:

• Daily dosing: 300 mg isoniazid + 600 mg rifampin once daily (7 days/week) 1
• Intermittent dosing: 900 mg isoniazid + 600 mg rifampin three times per week 1

These drugs require no frequency adjustment in renal failure because they are hepatically metabolized 1. Rifampin is not cleared by hemodialysis due to high molecular weight, wide tissue distribution, high protein binding, and rapid hepatic metabolism 1.

Pyrazinamide and Ethambutol (ZE)

Administer ONLY three times per week (not daily), post-dialysis:

• Pyrazinamide: 25-35 mg/kg per dose three times weekly 1
• Ethambutol: 15-25 mg/kg per dose three times weekly 1

These drugs accumulate in renal failure and require extended dosing intervals 1. PZA is significantly cleared by dialysis, while EMB is approximately 80% renally cleared 1.

Timing of Administration

All antitubercular drugs should be given AFTER hemodialysis on dialysis days to:

• Facilitate directly observed therapy (DOT) 1
• Avoid premature drug removal during dialysis 1
• Eliminate need for supplemental dosing 1

On non-dialysis days, HR can be given at any consistent time if using daily dosing.

Practical Regimen Structure

Option 1: Daily HR + Intermittent ZE

• Monday, Wednesday, Friday (post-dialysis): H 300 mg + R 600 mg + Z 25-35 mg/kg + E 15-25 mg/kg
• Tuesday, Thursday, Saturday, Sunday: H 300 mg + R 600 mg only

Option 2: All Drugs Intermittent

• Monday, Wednesday, Friday (post-dialysis): H 900 mg + R 600 mg + Z 25-35 mg/kg + E 15-25 mg/kg
• Tuesday, Thursday, Saturday, Sunday: No TB medications

The intermittent approach (Option 2) simplifies adherence and is the preferred strategy in dialysis populations 1.

Critical Monitoring Requirements

• Therapeutic drug monitoring should be considered to ensure adequate absorption without excessive accumulation 1
• Baseline and monthly assessments for hepatotoxicity, visual changes (ethambutol), and treatment response 1
• Increase dosing intervals rather than decrease individual doses to maintain peak concentrations and bactericidal efficacy 3

Common Pitfalls to Avoid

• Never use FDC tablets in dialysis patients—this is the single most important error to avoid 2
• Never reduce the milligram dose of individual drugs; only extend intervals 1, 3
• Never give medications before dialysis—always post-dialysis 1
• Never use daily dosing for pyrazinamide or ethambutol in dialysis patients—three times weekly only 1