What are the NTEP (National Tuberculosis Elimination Programme) guidelines for dosing of Anti-Tubercular (Anti-TB) drugs?

NTEP Guidelines on Dosing of Anti-Tubercular Drugs

The National Tuberculosis Elimination Programme (NTEP) recommends a standard 6-month regimen for drug-susceptible tuberculosis, consisting of 2 months of isoniazid, rifampicin, pyrazinamide, and ethambutol (intensive phase) followed by 4 months of isoniazid and rifampicin (continuation phase), with daily dosing being strongly preferred over intermittent dosing. 1

Standard First-Line Anti-TB Drug Dosages

Daily Dosing (Preferred)

• Isoniazid (H):

  • Adults: 5 mg/kg (maximum 300 mg) daily 1, 2
  • Children: 10-15 mg/kg (maximum 300 mg) daily 2

• Rifampicin (R):

  • Adults: 10 mg/kg (450 mg for <50 kg; 600 mg for >50 kg) daily 1
  • Children: 10-20 mg/kg daily 1, 2

• Pyrazinamide (Z):

  • Adults: 15-30 mg/kg (1.5 g for <50 kg; 2.0 g for >50 kg) daily 1, 3
  • Children: 15-30 mg/kg daily 3

• Ethambutol (E):

  • Adults and children: 15 mg/kg daily 1
  • Accurate calculation is essential to reduce risk of toxicity 1

Treatment Regimen Structure

Standard Regimen (2HRZE/4HR)

1. Intensive Phase (First 2 months):

   • Daily isoniazid, rifampicin, pyrazinamide, and ethambutol
   • If drug susceptibility results confirm sensitivity to isoniazid and rifampicin, ethambutol can be discontinued 1

2. Continuation Phase (Next 4 months):

   • Daily isoniazid and rifampicin 1

Special Considerations

Drug Resistance

• If isoniazid resistance is detected, continue rifampicin, ethambutol, and pyrazinamide for a full 6 months 4
• For multidrug-resistant TB (MDR-TB), treatment should be managed by specialists with experience in TB management 1

Special Populations

Pregnancy

• All first-line drugs except streptomycin can be used during pregnancy 4, 5
• Prophylactic pyridoxine (10 mg/day) is recommended 4, 5

HIV Co-infection

• Standard 6-month regimen is recommended, but response should be carefully monitored 6
• If response is slow or suboptimal, treatment duration should be extended 6
• Drug interactions between rifampicin and antiretroviral medications must be managed carefully 4, 5

Diabetes Mellitus

• Standard drug regimen is used, but strict blood glucose control is mandatory 5
• Doses of oral hypoglycemic agents may need to be increased due to interaction with rifampicin 5

Monitoring and Adherence

• Directly observed therapy (DOT) is strongly recommended to ensure adherence 1
• Fixed-dose combinations (FDCs) can minimize selective drug intake and improve adherence 5
• Regular monitoring for adverse effects is essential, including:
  • Hepatotoxicity (isoniazid, rifampicin, pyrazinamide)
  • Optic neuritis (ethambutol)
  • Peripheral neuropathy (isoniazid) - preventable with pyridoxine supplementation 1, 2

Important Clinical Considerations

• Pyridoxine (vitamin B6), 25-50 mg/day, should be given with isoniazid to all persons at risk of neuropathy (pregnant women, breastfeeding infants, persons with HIV, patients with diabetes, alcoholism, malnutrition, chronic renal failure, or advanced age) 1

• If positive culture for M. tuberculosis has been obtained but susceptibility results are pending after two months, continue pyrazinamide and ethambutol until full susceptibility is confirmed 1

• Treatment of all TB patients should be supervised by physicians with full training in TB management and with direct access to TB nurse specialists or health visitors 1