Should we use standard mg/kg dosing of Isoniazid (Isoniazid) or a fixed 300 mg/day dose for the treatment of tuberculosis (TB) in adults and pediatric patients?

Isoniazid Dosing: Weight-Based vs Fixed 300 mg Daily

We should use weight-based dosing of 5 mg/kg (maximum 300 mg) daily for isoniazid in tuberculosis treatment, not a fixed 300 mg dose for all patients. This approach ensures adequate drug exposure across different body weights while preventing toxicity in smaller patients.

Standard Adult Dosing

• The recommended dose is 5 mg/kg daily with a maximum of 300 mg for daily therapy 1, 2, 3, 4
• This weight-based approach is endorsed by the American Thoracic Society, American Academy of Family Physicians, and FDA labeling 1, 2, 4
• For intermittent therapy (twice or three times weekly), the dose increases to 15 mg/kg with a maximum of 900 mg, requiring direct observation 1, 3, 4

Pediatric Dosing Considerations

• Children require 10-15 mg/kg daily (maximum 300 mg) rather than the lower 5 mg/kg dose 3, 4, 5
• The British Thoracic Society historically recommended 5 mg/kg for children, but this produces inadequate serum concentrations 6
• Pharmacokinetic studies demonstrate that children prescribed 4-6 mg/kg achieve peak concentrations 58% lower than those receiving 8-10 mg/kg, with 70% of children on lower doses failing to reach therapeutic levels of 3 mg/L 5
• Younger children require higher per-kilogram doses because they have faster drug clearance and lower bioavailability compared to adults 5, 7

Why Weight-Based Dosing Matters

• A fixed 300 mg dose would result in overdosing for patients weighing less than 60 kg and underdosing for those weighing more than 60 kg 1, 2
• The 300 mg maximum exists specifically to prevent toxicity, particularly hepatotoxicity, which increases with higher absolute doses 6, 4
• Weight-based dosing ensures therapeutic drug levels while respecting safety thresholds across diverse patient populations 5, 7

Special Populations

• The same 5 mg/kg daily dosing (maximum 300 mg) applies to all forms of tuberculosis, including pulmonary, extrapulmonary, genitourinary, bone/joint, and disseminated disease 6, 1, 3, 4
• For TB meningitis, the weight-based dosing remains unchanged, but treatment duration extends to 12 months 6, 1, 2
• Pregnant women should receive the standard 5 mg/kg daily dose with pyridoxine 25-50 mg supplementation 1, 2

Critical Monitoring

• Pyridoxine supplementation (25-50 mg daily) is essential for pregnant/breastfeeding women, HIV-infected patients, malnourished patients, alcoholics, and diabetics to prevent peripheral neuropathy 1, 2, 4
• Baseline liver function tests are required in all adults, with monthly clinical assessments for adherence and adverse effects 1, 2
• Patients with chronic liver disease, alcoholism, or hepatitis B/C require weekly liver function monitoring for the first two weeks, then every two weeks during the initial two months 6

Common Pitfall to Avoid

• Do not prescribe a flat 300 mg dose to all patients regardless of weight—this abandons the pharmacokinetic rationale for weight-based dosing and risks both treatment failure in larger patients and toxicity in smaller patients 1, 2, 5