What is the recommended dose of isoniazid (Isoniazid) for the treatment of tuberculosis (TB)?

Isoniazid Dosing for Tuberculosis Treatment

For active tuberculosis treatment in adults, administer isoniazid 5 mg/kg (maximum 300 mg) daily, or 15 mg/kg (maximum 900 mg) twice or three times weekly under directly observed therapy. 1, 2

Adult Dosing Regimens

Daily Therapy

• 5 mg/kg up to 300 mg once daily is the standard dose for daily administration 1, 2
• This dosing applies to all standard 6-month short-course regimens for pulmonary and most extrapulmonary tuberculosis 1

Intermittent Therapy (Requires Direct Observation)

• 15 mg/kg up to 900 mg administered 2-3 times weekly 1, 2
• Must always be given as directly observed therapy (DOT) 1, 2
• Provides equivalent efficacy when adherence is assured 1

Pediatric Dosing

Daily Regimens

• 10-15 mg/kg (maximum 300 mg) once daily is recommended by most authorities 1, 2
• The British Thoracic Society recommends 5 mg/kg based on pharmacokinetic data showing adequate serum concentrations 1
• However, research demonstrates that younger children require higher doses (8-12 mg/kg) to achieve adult-equivalent drug concentrations, as children prescribed 4-6 mg/kg had 58% lower peak concentrations than those receiving 8-10 mg/kg 3

Intermittent Regimens

• 20-30 mg/kg (maximum 900 mg) twice weekly under direct observation 2
• 20-40 mg/kg (maximum 900 mg) 2-3 times weekly 2

Special Clinical Situations

HIV-Infected Patients

• Use the same weight-based dosing as HIV-negative patients 1, 2
• Critical caveat: Screening of antimycobacterial drug levels may be necessary in advanced HIV disease due to malabsorption issues 2
• This prevents emergence of multidrug-resistant TB 2

Extrapulmonary Tuberculosis

• Use standard 6-month regimen dosing (5 mg/kg daily) for most sites including genitourinary, bone/joint, and disseminated disease 1
• Exception: TB meningitis requires 12 months of therapy in children and adults, with the same weight-based dosing 1, 2

Drug-Resistant TB with inhA Mutations

• 10-15 mg/kg daily demonstrates bactericidal activity against isoniazid-resistant strains with inhA mutations similar to standard dosing against drug-sensitive strains 4
• This supports the use of high-dose isoniazid in multidrug-resistant TB regimens when inhA mutations are present 4

Treatment Duration and Completion

Standard Regimens

• 6 months total: 2 months of isoniazid, rifampin, pyrazinamide, and ethambutol, followed by 4 months of isoniazid and rifampin 1, 2
• Completion is based on total doses administered, not duration alone 1
• Daily therapy requires at least 217 doses over 6 months 1
• Twice-weekly therapy requires at least 62 doses over 6 months 1

Extended Duration Situations

• 12 months for TB meningitis, miliary TB in infants/children, and bone/joint TB in children due to insufficient data 1, 2
• 9 months for cerebral tuberculoma without meningitis 1

Pyridoxine Supplementation

• 25-50 mg daily should be administered to prevent peripheral neuropathy 5
• Mandatory for: pregnant women, breastfeeding infants, HIV-infected patients, malnourished patients, alcoholics, and diabetics 5, 2
• Not routinely necessary for well-nourished children except breast-fed infants 1

Critical Monitoring Requirements

Baseline Assessment

• Liver function tests (AST, ALT, bilirubin, alkaline phosphatase), serum creatinine, and platelet count in all adults 1
• Drug susceptibility testing for isoniazid, rifampin, and ethambutol on initial positive cultures 1
• HIV testing and CD4+ count if positive 1

Ongoing Monitoring

• Monthly clinical assessments for adherence and adverse effects throughout treatment 5
• Hepatotoxicity occurs in 10-20% (asymptomatic aminotransferase elevations) and clinical hepatitis in approximately 0.6% 5
• Regular liver function monitoring required for patients with chronic liver disease, alcoholism, hepatitis B/C, or pregnancy 1

Common Pitfalls to Avoid

• Do not use 4-6 mg/kg dosing in young children: This results in subtherapeutic concentrations in 70% of cases 3
• Do not omit the fourth drug (ethambutol) unless isoniazid resistance rate is documented <4% in the community 1, 2
• Do not use intermittent dosing without direct observation: Non-adherence is the major cause of drug-resistant TB 2
• Do not use ethambutol in unconscious patients or young children whose visual acuity cannot be monitored 1
• Acetylator status matters: Intermediate or fast acetylators have 38% lower peak concentrations than slow acetylators, though routine genotyping is not required as weight-based dosing accounts for this variability 3