TB Medication Dosing in India
For drug-susceptible tuberculosis in India, the standard regimen consists of isoniazid (5 mg/kg up to 300 mg), rifampicin (10 mg/kg up to 600 mg), pyrazinamide (15-30 mg/kg up to 2 g), and ethambutol (15-25 mg/kg) given daily for 2 months, followed by isoniazid and rifampicin for 4 months, with thrice-weekly intermittent dosing as an alternative under directly observed therapy. 1, 2, 3, 4
Standard First-Line Regimen
Initial Intensive Phase (2 months)
- Isoniazid: 5 mg/kg daily (maximum 300 mg) or 15 mg/kg thrice weekly (maximum 900 mg) 1, 4
- Rifampicin: 10 mg/kg daily (maximum 600 mg) or 10 mg/kg thrice weekly (maximum 600 mg) 2, 4
- Pyrazinamide: 15-30 mg/kg daily (maximum 2 g) or 50-70 mg/kg thrice weekly 3, 4
- Ethambutol: 15-25 mg/kg daily or 50 mg/kg thrice weekly 4
Continuation Phase (4 months)
India-Specific Dosing Considerations
The Revised National TB Control Programme in India has implemented higher-dose thrice-weekly intermittent therapy (2E₃H₃R₃Z₃, 4H₃R₃) as the standard approach, where drugs are given three times per week under directly observed therapy. 4 This differs from daily regimens used in many Western countries but aligns with WHO recommendations for resource-limited settings.
Weight-Based Dosing for Daily Regimens
For daily administration, ethambutol dosing follows these weight bands 5:
- 40-55 kg: 800 mg daily (14.5-20.0 mg/kg)
- 56-75 kg: 1200 mg daily (16.0-21.4 mg/kg)
- 76-90 kg: 1600 mg daily (17.8-21.1 mg/kg)
Pediatric Dosing
Indian children require careful dose optimization, as standard dosing often results in suboptimal drug concentrations, particularly for rifampicin in low-weight and HIV-coinfected children. 6
Standard Pediatric Doses
- Isoniazid: 10-15 mg/kg daily (maximum 300 mg) or 20-40 mg/kg thrice weekly (maximum 900 mg) 1, 4
- Rifampicin: 10-20 mg/kg daily (maximum 600 mg) or 10-20 mg/kg thrice weekly (maximum 600 mg) 2, 4
- Pyrazinamide: 15-30 mg/kg daily or 50-70 mg/kg thrice weekly 3, 4
- Ethambutol: 15-25 mg/kg daily or 50 mg/kg thrice weekly 4
Critical Pediatric Considerations
Children weighing 4-7 kg and those with HIV coinfection require 33% and 190% higher rifampicin doses respectively compared to standard guidelines to achieve adequate drug exposure and prevent treatment failure. 6 This is particularly important in India where malnutrition and HIV coinfection are common.
Special Populations
Pregnancy
All first-line drugs (rifampicin, isoniazid, ethambutol, pyrazinamide) can be used during pregnancy, but streptomycin must be avoided due to fetal ototoxicity. 4 Prophylactic pyridoxine 10 mg/day should be added to prevent isoniazid-induced peripheral neuropathy 4.
Diabetes Mellitus
The standard drug regimen is used, but strict glucose control is mandatory, and oral hypoglycemic doses may need to be increased due to rifampicin-induced metabolism. 4 Prophylactic pyridoxine is indicated 4.
Renal Failure
Dosages must be adjusted based on creatinine clearance, particularly for streptomycin, ethambutol, and isoniazid. 4 In acute renal failure, ethambutol should be given 8 hours before hemodialysis 4.
Pre-existing Liver Disease
In stable disease with normal liver enzymes, all anti-tuberculous drugs may be used, but frequent monitoring of liver function tests is required. 4 If liver enzymes are elevated, non-rifampicin regimens may be necessary 4.
HIV Coinfection
The usual short-course chemotherapy is indicated in HIV-positive patients, but relapse is more frequent. 4 Rifampicin-containing regimens interact with protease inhibitors and NNRTIs, requiring either postponement of antiretroviral therapy, use of modified doses, or selection of compatible antiretroviral combinations such as efavirenz 7, 4.
Fixed-Dose Combinations
Fixed-dose combinations (FDCs) consisting of two or three anti-tuberculosis medications provide a realistic alternative to directly observed therapy by minimizing the opportunity for selective medication intake. 4 These are widely used in India and include:
- Two-drug FDC: Isoniazid + Rifampicin
- Three-drug FDC: Isoniazid + Rifampicin + Pyrazinamide
- Four-drug FDC: Isoniazid + Rifampicin + Pyrazinamide + Ethambutol 7
Treatment Duration
The minimum duration is 6 months for drug-susceptible pulmonary tuberculosis, consisting of 2 months intensive phase followed by 4 months continuation phase. 7, 4 Extrapulmonary tuberculosis, including miliary TB, bone/joint TB, and tuberculous meningitis in children, should receive 12 months of therapy 4.
Critical Monitoring Requirements
Baseline Assessment
- Visual acuity testing using Snellen chart before starting ethambutol 5
- Liver function tests for all patients 7
- Renal function assessment 7
During Treatment
- Monthly questioning about visual disturbances (blurred vision, scotomata) for patients on ethambutol 5
- Liver function tests if symptoms develop or in patients with underlying liver disease 7
- Sputum smear and culture at 2-3 months to assess response 7
Common Pitfalls to Avoid
Patients who remain smear-positive at 3 months require immediate reevaluation for nonadherence or drug-resistant disease. 7 The high rate of acquired multidrug resistance in India (14% in Delhi, with only 1.4% primary resistance) indicates that most MDR-TB results from poor chemotherapy adherence 4.
Arthralgia occurs in 45-70% of patients on pyrazinamide-containing regimens but requires chemotherapy modification in only 5-12% of cases. 8 Jaundice occurs in approximately 7% of patients on rifampicin-containing regimens 8.
Ethambutol should not be used in young children whose visual acuity cannot be monitored, as dose-related retrobulbar neuritis is the primary safety concern. 5, 4