What is the appropriate number of isoniazid‑rifampicin‑pyrazinamide‑ethambutol (HRZE) tablets for a patient weighing 48 kg?

HRZE Dosing for 48 kg Patient

For a patient weighing 48 kg, administer 3 tablets of the standard fixed-dose combination (FDC) HRZE formulation daily, which provides rifampicin 450 mg, isoniazid 225 mg, pyrazinamide 1200 mg, and ethambutol 825 mg.

Weight-Band Dosing Strategy

The WHO weight-banded dosing approach places a 48 kg patient in the 40-55 kg weight band 1. However, the evidence shows important nuances:

• Standard FDC tablets typically contain rifampicin 150 mg, isoniazid 75 mg, pyrazinamide 400 mg, and ethambutol 275 mg per tablet 2
• For the 40-55 kg weight band, 3 tablets daily is the recommended dose 1
• This provides adequate exposure for all four drugs when using properly bioequivalent FDC formulations 2

Individual Drug Dose Verification

When using 3 FDC tablets for a 48 kg patient, the achieved doses are:

• Rifampicin: 450 mg (9.4 mg/kg) - within the recommended 8-12 mg/kg range 1
• Isoniazid: 225 mg (4.7 mg/kg) - within the recommended 4-6 mg/kg range 1
• Pyrazinamide: 1200 mg (25 mg/kg) - within the recommended 20-30 mg/kg range 1
• Ethambutol: 825 mg (17.2 mg/kg) - within the recommended 15-25 mg/kg range 1

Critical Considerations for Patients Near Weight Band Boundaries

Important caveat: A 48 kg patient is at the upper end of the 40-55 kg weight band. Research demonstrates that patients at weight band boundaries, particularly those under 55 kg, may achieve suboptimal drug exposures, especially for pyrazinamide 3. More than 50% of patients weighing less than 55 kg achieved lower pyrazinamide exposures than targeted 3.

• If using separate drug formulations rather than FDC tablets, consider adding 400 mg pyrazinamide to improve exposure for patients in the 30-54 kg range 3
• Monitor treatment response closely at 2 months with sputum smear microscopy 1

Duration and Phase-Specific Dosing

• Intensive phase: All four drugs (HRZE) for 2 months 1
• Continuation phase: Typically rifampicin and isoniazid only for 4 additional months 1
• Pyrazinamide should not be continued beyond 2 months in drug-susceptible TB 4

Monitoring Requirements

• Baseline liver function tests before initiating therapy 1
• Monthly monitoring for adherence and adverse effects 4
• Visual acuity testing at baseline when using ethambutol, particularly at doses >15 mg/kg 1
• If liver enzymes rise to 5 times normal or bilirubin rises, stop hepatotoxic drugs immediately 4

Common Pitfalls to Avoid

• Do not underdose patients near the upper weight band boundary - consider that 48 kg is close to 55 kg threshold and may benefit from closer monitoring 3
• Do not use FDC tablets for patients >90 kg without supplementing with additional tablets 4
• Do not continue pyrazinamide beyond 2 months even if extending total treatment duration 4
• Ensure bioequivalent FDC formulations are used, as substandard products may provide inadequate drug exposure 2