What is the dosing for Anti-Tuberculosis Treatment (ATT)?

Anti-Tuberculosis Treatment (ATT) Dosing Guidelines

The standard ATT regimen consists of isoniazid (H), rifampin (R), pyrazinamide (Z), and ethambutol (E) for the initial 2 months, followed by isoniazid and rifampin for 4 months, with specific weight-based dosing for each medication. 1, 2

First-Line Drug Dosing for Adults

Daily Dosing (Preferred)

• Isoniazid: 5 mg/kg (typically 300 mg) daily 1, 3
• Rifampin: 10 mg/kg (typically 600 mg) daily 1
• Pyrazinamide: 15-30 mg/kg daily (maximum 2g) 1, 4
• Ethambutol: 15-25 mg/kg daily 1

Intermittent Dosing (Three times weekly)

• Isoniazid: 15 mg/kg (typically 900 mg) 1, 3
• Rifampin: 10 mg/kg (typically 600 mg) 1
• Pyrazinamide: 30-40 mg/kg 1
• Ethambutol: 25-35 mg/kg 1

First-Line Drug Dosing for Children

Daily Dosing

• Isoniazid: 10-15 mg/kg daily 1, 2
• Rifampin: 10-20 mg/kg daily 1, 2
• Pyrazinamide: 35 mg/kg daily 1, 2
• Ethambutol: 20 mg/kg daily 1, 2

Treatment Duration

The standard treatment duration for drug-susceptible pulmonary tuberculosis is 6 months:

• Initial phase: 2 months of HRZE
• Continuation phase: 4 months of HR 1

Special situations requiring longer treatment:

• TB meningitis/CNS TB: 12 months (2 months HRZE + 10 months HR) 1
• Bone/joint TB in children: 12 months 1
• Military TB in children: 12 months 1

Treatment Categories

WHO categorizes TB treatment into four groups 1:

1. Category I: New sputum smear-positive and other severe cases
2. Category II: Retreatment cases
3. Category III: New sputum smear-negative and non-severe extrapulmonary cases
4. Category IV: Chronic cases

Retreatment Regimens

For previously treated patients who are more likely to have acquired drug resistance:

• Initial phase: 5 drugs (SHRZE) for 2 months, followed by 4 drugs (HRZE) for 1 month
• Continuation phase: 3 drugs (HRE) for 5 months 1

Fixed-Dose Combinations (FDCs)

FDCs are strongly recommended to improve adherence 1:

• Rifamate®: Each capsule contains rifampin (300 mg) and isoniazid (150 mg); daily dose is two capsules 1
• Rifater®: Each tablet contains rifampin (120 mg), isoniazid (50 mg), and pyrazinamide (300 mg); dosing based on weight 1

Special Considerations

Pregnancy

• All drugs except streptomycin can be used during pregnancy
• Pyridoxine (vitamin B6) 10-25 mg/day is recommended with isoniazid 1, 3

Renal Insufficiency

• Dosage adjustments needed for ethambutol and streptomycin
• Rifamate® may be used, but Rifater® should be avoided 1

Hepatic Disease

• In patients with underlying hepatic disease, single-drug formulations are preferred until safety is established 1

HIV Co-infection

• Standard regimens are effective but may require longer treatment
• Monitor for drug interactions with antiretroviral therapy 1

Directly Observed Therapy (DOT)

DOT is strongly recommended to ensure adherence and prevent drug resistance 3. This involves:

• Direct observation of medication intake by healthcare personnel
• Can be administered daily or intermittently (3 times weekly)

Monitoring

• Regular assessment of treatment response through clinical evaluation and sputum examinations
• Monitor for adverse effects, especially hepatotoxicity
• Adjust dosages with significant weight changes during treatment 2

Pitfalls to Avoid

1. Inadequate initial regimen: Always include at least 4 drugs in the initial phase until susceptibility is confirmed
2. Inappropriate intermittent therapy: Intermittent therapy should only be used with DOT
3. Failure to adjust doses for weight: Recalculate doses with significant weight changes
4. Overlooking drug interactions: Particularly important with rifampin
5. Inadequate treatment duration: Shortened regimens have been shown to increase relapse rates 5

Remember that proper dosing and adherence to the full treatment course are essential to prevent treatment failure and development of drug resistance.