How do you calculate HRZE (isoniazid, rifampicin, pyrazinamide, ethambutol) dosage for a tuberculosis patient based on weight?

Weight-Based Dosing for HRZE in Tuberculosis

HRZE dosing should be calculated using weight-banded dosing tables that account for lean body weight, with specific milligram amounts assigned to weight ranges rather than simple mg/kg calculations, to ensure adequate drug exposure while minimizing toxicity risk. 1, 2

Standard Weight-Banded Dosing for Adults

The British Thoracic Society and American Thoracic Society recommend the following weight-banded approach for daily dosing 1:

Isoniazid (H)

• All adults: 300 mg daily (approximately 5 mg/kg) 1
• Children: 5 mg/kg daily (maximum 300 mg) 1
• Intermittent dosing: 15 mg/kg three times weekly (maximum 900 mg) 1

Rifampicin (R)

• <50 kg: 450 mg daily 1
• ≥50 kg: 600 mg daily 1
• Children: 10 mg/kg daily 1
• Intermittent dosing: 600 mg three times weekly for adults >50 kg 1

Pyrazinamide (Z)

• 40-55 kg: 1,000 mg daily (18.2-25.0 mg/kg) 2
• 56-75 kg: 1,500 mg daily (20.0-26.8 mg/kg) 2
• 76-90 kg: 2,000 mg daily (22.2-26.3 mg/kg) 2
• Maximum daily dose: 2,000 mg regardless of weight 2, 3
• Children: 15-30 mg/kg daily (maximum 2 g) 3

Ethambutol (E)

• 40-55 kg: 800 mg daily (14.5-20.0 mg/kg) 1
• 56-75 kg: 1,200 mg daily (16.0-21.4 mg/kg) 1
• 76-90 kg: 1,600 mg daily (17.8-21.1 mg/kg) 1
• Children: 15-25 mg/kg daily 1

Critical Dosing Principles

Accurate calculation based on lean body weight is essential, particularly for ethambutol to reduce toxicity risk and for pyrazinamide to ensure adequate exposure 1. The CDC emphasizes that dosing should be based on lean body weight, not total body weight, especially in obese patients 2.

Patients at the upper end of a weight band should receive the higher dose to ensure adequate drug exposure and prevent treatment failure 2. For example, a patient weighing 74 kg (close to the 76 kg threshold) should receive pyrazinamide 2,000 mg daily rather than 1,500 mg 2.

Intermittent Dosing Schedules

For twice-weekly directly observed therapy (DOT), higher doses are required 1, 2:

Twice Weekly Dosing

• Isoniazid: 15 mg/kg (maximum 900 mg) 1
• Rifampicin: 600 mg for adults >50 kg 1
• Pyrazinamide 40-55 kg: 2,000 mg (36.4-50.0 mg/kg) 2
• Pyrazinamide 56-75 kg: 3,000 mg (40.0-53.6 mg/kg) 2
• Pyrazinamide 76-90 kg: 4,000 mg (44.4-52.6 mg/kg) 2
• Ethambutol 40-55 kg: 2,000 mg 1
• Ethambutol 56-75 kg: 2,800 mg 1
• Ethambutol 76-90 kg: 4,000 mg 1

Three Times Weekly Dosing

• Isoniazid: 15 mg/kg (maximum 900 mg) 1
• Rifampicin: 600 mg for adults >50 kg 1
• Pyrazinamide 40-55 kg: 1,500 mg 2
• Pyrazinamide 56-75 kg: 2,500 mg 2
• Pyrazinamide 76-90 kg: 3,000 mg 2
• Ethambutol: 30 mg/kg 1

Special Population Adjustments

HIV-infected patients with CD4 <100/μL should receive daily or three times weekly dosing, not twice weekly, due to higher treatment failure rates with less frequent dosing 1. Daily dosing is strongly preferred over intermittent therapy when feasible 4.

Pediatric patients require higher mg/kg doses than adults: isoniazid 10-20 mg/kg (vs 5 mg/kg in adults), rifampicin 10-20 mg/kg (vs 10 mg/kg), and pyrazinamide 15-30 mg/kg 3, 5.

Patients with renal failure require dose adjustments for ethambutol and isoniazid based on creatinine clearance, while rifampicin and pyrazinamide doses remain unchanged 6.

Pregnant women can receive all four drugs at standard doses, but streptomycin should be avoided due to fetal ototoxicity 6. Pyridoxine 10 mg daily should be added to prevent peripheral neuropathy 6.

Common Pitfalls to Avoid

Never use simple mg/kg calculations without checking against weight-banded tables, as this can lead to underdosing (treatment failure) or overdosing (toxicity) 1, 2. The weight bands are designed to balance efficacy and safety.

Do not omit ethambutol in the initial phase unless drug susceptibility is confirmed and primary isoniazid resistance is <4% in the community 1, 5. The fourth drug protects against unrecognized isoniazid resistance.

Fixed-dose combination tablets may not provide adequate dosing for patients >90 kg, requiring additional individual drug tablets to achieve target doses 2.

Pyrazinamide should not be continued beyond 2 months in drug-susceptible TB, even if extending total treatment duration, as prolonged use increases hepatotoxicity without additional benefit 2, 4.

For patients unable to swallow, drugs may be crushed and administered via nasogastric tube, or parenteral alternatives (intramuscular streptomycin and isoniazid, intravenous quinolones) can be used temporarily 6.