What are the recommended doses of antitubercular (anti-tuberculosis) drugs, including isoniazid, rifampicin, pyrazinamide, and ethambutol, for a typical adult patient with normal liver and renal function?

Antitubercular Drug Dosing for Adults with Normal Hepatic and Renal Function

Standard Daily Dosing Regimen

For typical adults with drug-susceptible tuberculosis and normal organ function, the recommended daily doses are: isoniazid 5 mg/kg (maximum 300 mg), rifampin 10 mg/kg (maximum 600 mg), pyrazinamide weight-based dosing per tables below, and ethambutol weight-based dosing per tables below. 1

First-Line Drug Doses - Daily Administration

• Isoniazid: 5 mg/kg daily, typically 300 mg maximum 1, 2
• Rifampin: 10 mg/kg daily, typically 600 mg maximum 1
• Pyrazinamide: Weight-based dosing varies by guideline 1, 3:
  • 40-55 kg: 1000 mg daily
  • 56-75 kg: 1500 mg daily
  • 76-90 kg: 2000 mg daily (maximum)
  • Alternative dosing: 15-30 mg/kg daily, not exceeding 2000 mg 3
• Ethambutol: Weight-based dosing 1:
  • 40-55 kg: 800 mg daily
  • 56-75 kg: 1200 mg daily
  • 76-90 kg: 1600 mg daily (maximum)
  • Alternative: 15-25 mg/kg daily 1

Intermittent Dosing Options

Twice-weekly dosing (administered by directly observed therapy only) 1:

• Isoniazid: 15 mg/kg, maximum 900 mg 1
• Rifampin: 10 mg/kg, maximum 600 mg 1
• Pyrazinamide: 50-70 mg/kg 1, 3:
  • 40-55 kg: 2000 mg
  • 56-75 kg: 3000 mg
  • 76-90 kg: 3500 mg
• Ethambutol: 50 mg/kg 1:
  • 40-55 kg: 2000 mg
  • 56-75 kg: 2800 mg
  • 76-90 kg: 4000 mg

Three-times-weekly dosing (administered by directly observed therapy only) 1:

• Isoniazid: 15 mg/kg, maximum 900 mg 1
• Rifampin: 10 mg/kg, maximum 600 mg 1
• Pyrazinamide: 50-70 mg/kg 1:
  • 40-55 kg: 1500 mg
  • 56-75 kg: 2500 mg
  • 76-90 kg: 3000 mg
• Ethambutol: 30 mg/kg 1:
  • 40-55 kg: 1200 mg
  • 56-75 kg: 2000 mg
  • 76-90 kg: 2400 mg

Standard Treatment Regimen Structure

The standard 6-month regimen consists of a 2-month intensive phase with all four drugs (isoniazid, rifampin, pyrazinamide, ethambutol), followed by a 4-month continuation phase with isoniazid and rifampin only. 1, 4

• The intensive phase uses all four first-line drugs to rapidly reduce bacterial burden 1
• Ethambutol can be discontinued once drug susceptibility testing confirms susceptibility to isoniazid and rifampin 1
• The continuation phase extends to 7 months (instead of 4 months) only for patients with cavitary disease whose sputum culture remains positive at 2 months 1

Critical Dosing Considerations

Pyridoxine (vitamin B6) supplementation at 25-50 mg daily must be given with isoniazid to all patients at risk of neuropathy, including pregnant women, breastfeeding infants, HIV-infected persons, and patients with diabetes, alcoholism, malnutrition, chronic renal failure, or advanced age. 1

Daily administration is preferred over intermittent dosing for both intensive and continuation phases, as it provides more consistent drug exposure and better outcomes. 1

Five-days-per-week administration by directly observed therapy is an acceptable alternative to 7-days-per-week administration based on extensive clinical experience, though not formally compared in trials. 1

Maximum daily doses exist to prevent toxicity and must not be exceeded: isoniazid 300 mg daily (900 mg intermittent), rifampin 600 mg, pyrazinamide 2000 mg daily (3000-3500 mg intermittent), and ethambutol 1600 mg daily (4000 mg intermittent). 1, 4, 3

Second-Line Drug Dosing

For patients requiring second-line agents due to intolerance or resistance 1:

• Levofloxacin: 500-1000 mg daily (750 mg preferred) 1
• Moxifloxacin: 400 mg daily 1
• Cycloserine: 10-15 mg/kg total daily (usually 250-500 mg once or twice daily) 1
• Ethionamide: 15-20 mg/kg total daily (usually 250-500 mg once or twice daily) 1
• Streptomycin: 15 mg/kg daily IM/IV (some prefer 25 mg/kg three times weekly) 1
• Amikacin/Kanamycin: 15 mg/kg daily IM/IV 1
• Capreomycin: 15 mg/kg daily IM/IV 1
• Para-aminosalicylic acid: 8-12 g total daily (usually 4000 mg 2-3 times daily) 1

Common Pitfalls to Avoid

Never use intermittent dosing without directly observed therapy, as unsupervised intermittent dosing leads to treatment failure and drug resistance. 1

Do not reduce doses in an attempt to minimize toxicity in patients with normal organ function, as subtherapeutic dosing is the primary driver of acquired drug resistance. 1

Avoid using pyrazinamide for twice-weekly or once-weekly regimens, as it is not recommended for these schedules. 1

Do not use rifapentine for twice-weekly or three-times-weekly dosing during the intensive phase, as inadequate data support these schedules. 1