What is the recommended dosage of tuberculosis (TB) medication per kilogram (kg) of body weight?

TB Medication Dosing Per Kilogram Body Weight

For drug-susceptible tuberculosis in adults, use isoniazid 5 mg/kg (max 300 mg), rifampin 10 mg/kg (max 600 mg), pyrazinamide 15-30 mg/kg (max 2000 mg), and ethambutol 15-25 mg/kg (max 2500 mg) daily. 1

First-Line Drug Dosing for Adults

Daily Therapy

• Isoniazid: 5 mg/kg (typically 300 mg maximum) 1, 2
• Rifampin: 10 mg/kg (typically 600 mg maximum) 1
• Pyrazinamide: 15-30 mg/kg daily (maximum 2000 mg per CDC recommendations, though some guidelines allow up to 3000 mg) 1, 3
• Ethambutol: 15-25 mg/kg (maximum 2500 mg) 1
• Streptomycin: 15 mg/kg daily (maximum 1000 mg) 1

Intermittent Therapy (Thrice-Weekly)

• Isoniazid: 15 mg/kg (typically 900 mg maximum) 1
• Rifampin: 10 mg/kg (typically 600 mg maximum) 1
• Pyrazinamide: 35 mg/kg (range 30-40 mg/kg) 1
• Ethambutol: 30 mg/kg (range 25-35 mg/kg) 1
• Streptomycin: 15 mg/kg (range 12-18 mg/kg) 1

Intermittent Therapy (Twice-Weekly)

• Isoniazid: 15 mg/kg (typically 900 mg maximum) 1
• Rifampin: 10 mg/kg (typically 600 mg maximum) 1
• Pyrazinamide: 50 mg/kg (range 40-60 mg/kg) 1
• Ethambutol: 45 mg/kg (range 40-50 mg/kg) 1

Pediatric Dosing

Daily Therapy in Children

• Isoniazid: 10-15 mg/kg (maximum 300 mg) 1
• Rifampin: 10-20 mg/kg (maximum 600 mg) 1
• Pyrazinamide: 35 mg/kg (range 30-40 mg/kg, maximum 2000 mg) 1
• Ethambutol: 20 mg/kg (range 15-25 mg/kg, maximum 2500 mg) 1
• Streptomycin: 20-40 mg/kg (maximum 1000 mg) 1

Intermittent Therapy in Children (Twice-Weekly)

• Isoniazid: 20-30 mg/kg (maximum 900 mg) 1
• Rifampin: 10-20 mg/kg (maximum 600 mg) 1
• Pyrazinamide: 50 mg/kg (maximum 3000 mg) 1
• Ethambutol: 50 mg/kg (maximum 2500 mg) 1

Retreatment Cases

For previously treated patients with higher risk of drug resistance, WHO recommends the following daily doses 1:

• Isoniazid: 5 mg/kg (range 4-6 mg/kg)
• Rifampin: 10 mg/kg (range 8-12 mg/kg)
• Pyrazinamide: 25 mg/kg (range 20-30 mg/kg)
• Streptomycin: 15 mg/kg (range 12-18 mg/kg)
• Ethambutol: 15 mg/kg (range 15-25 mg/kg), though some recommend 25 mg/kg during intensive phase followed by 15 mg/kg during continuation phase 1

Second-Line Drugs

For drug-resistant tuberculosis 1:

• Cycloserine: 10-15 mg/kg total daily (usually 250-500 mg once or twice daily)
• Ethionamide: 15-20 mg/kg total daily (usually 250-500 mg once or twice daily)
• Amikacin/Kanamycin/Capreomycin: 15 mg/kg daily (some prefer 25 mg/kg three times weekly)
• Para-aminosalicylic acid: 8-12 g total daily in adults (200-300 mg/kg in children)
• Levofloxacin: 500-1000 mg daily (15-20 mg/kg in children)
• Moxifloxacin: 400 mg daily in adults (10 mg/kg in children)

Critical Dosing Considerations

Weight-Based Adjustments

Dosing should be based on actual body weight for non-obese patients, but ideal body weight or modified ideal body weight for obese patients (>20% above ideal body weight). 1 Recent evidence shows that patients with higher body mass index often receive inadequate doses per kilogram, leading to suboptimal drug exposure 4.

Pyridoxine Supplementation

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

Common Pitfalls

• Suboptimal exposure is common: Studies show 60-66% of patients have suboptimal rifampin concentrations and 54-55% have suboptimal isoniazid concentrations with standard dosing 4
• Higher doses may be needed: Research suggests current rifampin doses may be too low, with doses up to 35 mg/kg being studied 1, 5
• Pyrazinamide dosing varies: The FDA label allows up to 3000 mg daily, but CDC recommendations cap at 2000 mg daily 3
• Renal impairment: Doses of streptomycin, ethambutol, and isoniazid require adjustment based on creatinine clearance 1, 6
• Hepatic impairment: In stable liver disease with normal enzymes, standard doses can be used with frequent monitoring 1, 6

HIV Co-infection

Standard short-course chemotherapy doses are appropriate for HIV-positive patients, though response monitoring is critical and therapeutic drug monitoring may be necessary due to malabsorption risk 1, 6.