What is the recommended treatment regimen for tuberculosis (TB) using Isoniazid?

Isoniazid Treatment Regimens for Tuberculosis

Active Tuberculosis Treatment

For active pulmonary tuberculosis, the preferred regimen is a 6-month course consisting of isoniazid, rifampin, pyrazinamide, and ethambutol for 2 months, followed by isoniazid and rifampin for 4 months. 1

Initial Phase (2 Months)

• Four-drug regimen: Isoniazid 5 mg/kg (maximum 300 mg) daily, rifampin, pyrazinamide, and ethambutol 1, 2
• Ethambutol can be omitted only if isoniazid resistance is less than 4% in the community AND the patient has no prior tuberculosis treatment, no exposure to drug-resistant cases, and is not from a high-prevalence country 1, 3
• Alternative dosing schedules: Daily for 2 weeks followed by twice-weekly for 6 weeks, or three times weekly throughout the initial phase 1
• Children: 10-15 mg/kg isoniazid (maximum 300 mg) daily 1, 2

Continuation Phase (4 Months)

• Two-drug regimen: Isoniazid and rifampin given daily or 2-3 times weekly 1
• Extended 7-month continuation phase required for: Patients with cavitary disease who remain culture-positive at 2 months, those whose initial phase excluded pyrazinamide, or those receiving once-weekly isoniazid-rifapentine who were culture-positive at 2 months 1

Alternative 9-Month Regimen

• Isoniazid and rifampin for 9 months (with ethambutol initially) is acceptable for patients who cannot tolerate pyrazinamide 1, 3
• If isoniazid resistance is confirmed, continue rifampin and ethambutol for minimum 12 months 3

Latent Tuberculosis Infection Treatment

The preferred regimen for latent tuberculosis is 9 months of daily isoniazid at 5 mg/kg (maximum 300 mg), which provides over 90% efficacy when completed. 1, 4

Primary Regimen Options

• 9 months daily isoniazid: Optimal protection, strongly recommended for HIV-infected persons 1, 4
• 6 months daily isoniazid: Provides substantial protection but less than 9 months; acceptable alternative 1, 4
• Twice-weekly dosing: 15 mg/kg (maximum 900 mg) under directly observed therapy for 9 months 1, 2

Alternative Regimens for Latent TB

• 4 months rifampin monotherapy: 10 mg/kg (maximum 600 mg) daily—superior completion rates, lower hepatotoxicity, clinically equivalent efficacy to 9 months isoniazid 5, 6
• 3 months weekly isoniazid-rifapentine (3HP): 12 doses total, equivalent efficacy with lower hepatotoxicity 5
• 2 months rifampin-pyrazinamide: Effective in HIV-infected persons but use with extreme caution in HIV-negative individuals due to severe hepatotoxicity risk 1, 5

Special Populations

HIV-Infected Patients

• Use standard 6-month four-drug regimen for active tuberculosis 1
• Critical monitoring required: Assess clinical and bacteriologic response closely; prolong therapy if slow or suboptimal response 3
• For latent TB: 9 months isoniazid preferred over 6 months 1, 4
• Consider rifabutin (150 mg daily) instead of rifampin when concurrent protease inhibitors or NNRTIs are used 1

Pregnant Women

• All first-line drugs (isoniazid, rifampin, ethambutol, pyrazinamide) can be used during pregnancy 2, 7
• Avoid streptomycin due to fetal ototoxicity 7
• Mandatory pyridoxine supplementation: 25-50 mg daily to prevent peripheral neuropathy 1, 7

Children

• Daily dosing: 10-15 mg/kg isoniazid (maximum 300 mg) 1, 2
• Twice-weekly: 20-40 mg/kg (maximum 900 mg) 2
• Manage essentially the same as adults with dose adjustments 3
• Exception: Miliary tuberculosis, bone/joint tuberculosis, or tuberculous meningitis requires minimum 12 months therapy 3

Patients with Diabetes or Renal Failure

• Same drug regimen as non-diabetic patients 7
• Adjust doses of streptomycin, ethambutol, and isoniazid based on creatinine clearance in renal failure 7
• Prophylactic pyridoxine indicated 7

Hepatotoxicity Monitoring

Baseline liver function testing is required for patients with HIV infection, chronic liver disease, regular alcohol use, pregnancy, or immediate postpartum period. 4

Risk Stratification

• Isoniazid alone: 0.6% clinical hepatitis rate 1
• Isoniazid plus rifampin: 2.7% clinical hepatitis rate 1
• Risk increases with age: uncommon under age 20, nearly 2% in ages 50-64 1
• Fatal hepatitis: 0.023% or lower 1

Management of Elevated Transaminases

• If AST/ALT 2-5 times normal: Monitor weekly for 2 weeks, then biweekly until normal 1
• If AST/ALT ≥5 times normal or bilirubin elevated: Stop rifampin, isoniazid, and pyrazinamide immediately 1
• For smear-positive patients, use streptomycin and ethambutol until liver function normalizes 1
• Sequential reintroduction: Start isoniazid 50 mg daily, increase to 300 mg over 2-3 days; add rifampin 75 mg, increase to full dose; finally add pyrazinamide 250 mg, increase to full dose 1

Clinical Monitoring

• Monthly clinical evaluations assessing for fever, malaise, vomiting, jaundice, or unexplained deterioration 1, 5
• Stop treatment immediately if hepatitis symptoms develop 1

Critical Implementation Points

Directly Observed Therapy (DOT)

• Strongly consider DOT for all patients to ensure adherence 1, 3
• All twice-weekly and three-times-weekly regimens must be given by DOT 1, 2

Drug Susceptibility Testing

• Perform on all initial isolates from newly diagnosed patients 2, 3
• If resistance develops, change to agents showing susceptibility 2

Fixed-Dose Combinations

• Rifater (isoniazid 50 mg, rifampin 120 mg, pyrazinamide 300 mg per tablet) provides convenient dosing and compliance monitoring through urine color 1, 8
• Bioavailability equivalent to individual drugs 1

Pyridoxine Supplementation

• Mandatory for all HIV-infected patients: 25-50 mg daily or 50-100 mg twice weekly 1
• Recommended for pregnant women, diabetics, and those with renal failure 1, 7