What is the standard dose of Isoniazid (INH) in milligrams per kilogram per day for the treatment of tuberculosis in adults and children?

Standard Isoniazid Dosing for Tuberculosis

For adults with tuberculosis, the standard dose of isoniazid is 5 mg/kg daily (maximum 300 mg) for daily therapy, or 15 mg/kg (maximum 900 mg) for intermittent twice- or three-times-weekly directly observed therapy. 1, 2, 3

Adult Dosing Regimens

Daily Therapy

• Administer isoniazid 5 mg/kg once daily with a maximum dose of 300 mg 4, 1, 3
• This dosing applies to all forms of tuberculosis including pulmonary, extrapulmonary (genitourinary, bone/joint, disseminated), and pleural disease 4, 1
• The dose can be given as a single daily administration or in two divided doses 4

Intermittent Therapy (Directly Observed)

• For twice-weekly dosing: 15 mg/kg (maximum 900 mg) 2, 3
• For three-times-weekly dosing: 15 mg/kg (maximum 900 mg) 4, 2, 3
• Intermittent therapy requires substantially higher per-kilogram doses to maintain therapeutic drug levels and must be administered under direct observation 2, 3

Pediatric Dosing

Current Guideline Recommendations

• The British Thoracic Society recommends 5 mg/kg daily for children based on pharmacokinetic data showing adequate serum concentrations 4, 1
• However, more recent guidelines suggest 10-15 mg/kg daily (maximum 300 mg) for children 2, 3

Important Pediatric Dosing Considerations

• For intermittent pediatric therapy: 20-40 mg/kg (maximum 900 mg) twice weekly 4, 2, 3
• Research evidence demonstrates that 5 mg/kg dosing in children produces lower serum concentrations than in adults, particularly in children younger than 8 years 5
• Studies suggest dosing based on body surface area (200 mg/m²) achieves more comparable serum levels to adults than weight-based dosing 5

A critical pitfall: The pediatric dosing recommendations have evolved, with older guidelines (1998-1999) recommending 5 mg/kg while newer evidence and FDA labeling support 10-15 mg/kg daily. 4, 3, 5

Special Clinical Situations

Tuberculosis Meningitis

• Use the same weight-based dosing (5 mg/kg daily for adults, 10-15 mg/kg for children) but extend treatment duration to 12 months 1

Pregnancy and Lactation

• The standard 5 mg/kg daily dose is safe and recommended during pregnancy 1, 6
• Add pyridoxine 25-50 mg daily to prevent peripheral neuropathy 1

HIV Co-infection

• Use standard dosing (5 mg/kg daily), but monitor for malabsorption which may require drug level screening 3, 6

Renal Insufficiency

• Dosing adjustments for isoniazid are generally not required in renal failure, unlike ethambutol and streptomycin 6
• Prophylactic pyridoxine is indicated 6

Diabetes Mellitus

• Use standard dosing with strict glucose control and prophylactic pyridoxine 6

Drug-Resistant Tuberculosis

Isoniazid-Resistant TB (inhA Mutations)

• For multidrug-resistant TB with inhA mutations, high-dose isoniazid at 10-15 mg/kg daily (maximum dose not specified in guidelines for this indication) demonstrates bactericidal activity 7, 8
• The optimal dose depends on N-acetyltransferase 2 (NAT2) acetylator status: 10 mg/kg for slow acetylators and 15 mg/kg for intermediate acetylators 7
• Fast acetylators may underperform even at 15 mg/kg 7

Critical caveat: High-dose isoniazid for drug-resistant TB should only be used in specialized centers with drug susceptibility testing and experience managing MDR-TB. 6

Essential Monitoring and Supplementation

Pyridoxine Supplementation

• Administer pyridoxine 25-50 mg daily to prevent peripheral neuropathy, particularly in:
  • Pregnant and breastfeeding women 1
  • HIV-infected patients 1
  • Malnourished patients 1
  • Alcoholics 1
  • Diabetics 1, 6

Baseline and Ongoing Monitoring

• Obtain baseline liver function tests, serum creatinine, and platelet count in all adults 1
• Perform monthly clinical assessments for adherence and adverse effects 1
• Regular liver function monitoring is required for patients with chronic liver disease, alcoholism, hepatitis B/C, or pregnancy 1

Treatment Duration and Completion

• The standard regimen is 6 months total: 2 months of isoniazid, rifampin, pyrazinamide, and ethambutol (intensive phase), followed by 4 months of isoniazid and rifampin (continuation phase) 1, 3
• Treatment completion is based on total doses administered (at least 217 doses over 6 months for daily therapy), not duration alone 1