Anti-Tubercular Drug Dosing
For drug-susceptible tuberculosis in adults, use isoniazid 5 mg/kg (max 300 mg), rifampin 10 mg/kg (max 600 mg), pyrazinamide 15-30 mg/kg (max 2000 mg), and ethambutol 15-25 mg/kg (max 2500 mg) daily; for children, use isoniazid 10-15 mg/kg (max 300 mg), rifampin 10-20 mg/kg (max 600 mg), pyrazinamide 30-40 mg/kg (max 2000 mg), and ethambutol 15-25 mg/kg (max 2500 mg) daily. 1, 2, 3, 4
Drug-Susceptible TB: First-Line Agents
Daily Dosing Regimen
Adults:
- Isoniazid: 5 mg/kg daily (maximum 300 mg) 1, 2, 4
- Rifampin: 10 mg/kg daily (maximum 600 mg) 1, 2, 3
- Pyrazinamide: 15-30 mg/kg daily (maximum 2000 mg per CDC; 3000 mg per FDA label) 1, 2, 5
- Ethambutol: 15-25 mg/kg daily (maximum 2500 mg) 1, 2
Children:
- Isoniazid: 10-15 mg/kg daily (maximum 300 mg) 1, 2, 4
- Rifampin: 10-20 mg/kg daily (maximum 600 mg) 1, 2, 3
- Pyrazinamide: 30-40 mg/kg daily (maximum 2000 mg) 1, 2
- Ethambutol: 15-25 mg/kg daily (maximum 2500 mg) 1, 2
Intermittent Dosing (Twice-Weekly)
Adults:
- Isoniazid: 15 mg/kg (maximum 900 mg) 1, 2
- Rifampin: 10 mg/kg (maximum 600 mg) 1, 2
- Pyrazinamide: 50-70 mg/kg 1, 5
- Ethambutol: 50 mg/kg 1, 2
Children:
- Isoniazid: 20-30 mg/kg (maximum 900 mg) 1, 2
- Rifampin: 10-20 mg/kg (maximum 600 mg) 1, 2
- Pyrazinamide: 50-70 mg/kg (maximum 3000 mg) 1, 2
- Ethambutol: 50 mg/kg (maximum 2500 mg) 1, 2
Intermittent Dosing (Thrice-Weekly)
Adults:
- Isoniazid: 15 mg/kg (maximum 900 mg) 1, 2
- Rifampin: 10 mg/kg (maximum 600 mg) 1, 2
- Pyrazinamide: 30-40 mg/kg 1
- Ethambutol: 25-35 mg/kg 1
Multidrug-Resistant TB: Second-Line Agents
Group 1: Fluoroquinolones (Highest Priority)
- Levofloxacin: 750-1000 mg daily in adults; 15-20 mg/kg daily in children 1, 2
- Moxifloxacin: 400 mg daily in adults (some use 600-800 mg); 10-15 mg/kg daily in children 1, 2
Group 2: Newer Agents
- Bedaquiline: 400 mg daily for 14 days, then 200 mg three times weekly in adults and children >12 years and >30 kg; for children 6-12 years and 15-30 kg, use half the adult dose (200 mg daily for 2 weeks, then 100 mg three times weekly) 1
- Linezolid: 600 mg daily in adults and children >12 years (10 mg/kg); for children <12 years, use weight-based dosing: 5-9 kg: 15 mg/kg, 10-23 kg: 12 mg/kg, >23 kg: 10 mg/kg 1
Group 3: Other Core Agents
- Clofazimine: 100 mg daily in adults; 2-5 mg/kg daily in children 1, 2
- Cycloserine/Terizidone: 15-20 mg/kg daily (usually 250-500 mg once or twice daily) in adults; 15-20 mg/kg daily in children 1, 2
Group 4: Injectable Agents
- Amikacin: 15 mg/kg daily (some prefer 25 mg/kg three times weekly) in adults; 15-20 mg/kg daily in children 1, 2
- Streptomycin: 15 mg/kg daily (some prefer 25 mg/kg three times weekly) in adults; 15-20 mg/kg daily or 25-30 mg/kg twice weekly in children 1, 2
Group 5: Additional Agents
- Delamanid: 100 mg twice daily in adults and children >35 kg; 50 mg twice daily for children 6+ years and 20-34 kg; 25 mg twice daily for children 3-5 years and 10-20 kg 1
- Ethionamide/Prothionamide: 15-20 mg/kg total daily (usually 250-500 mg once or twice daily) in adults; 15-20 mg/kg total daily (divided 1-2 times daily) in children 1, 2
Critical Dosing Considerations
Weight-Based Adjustments
Dosing should be based on actual body weight for non-obese patients. For obese patients (>20% above ideal body weight), use ideal body weight or modified ideal body weight (IBW + [0.40 × (actual weight – IBW)]) for initial dosing, with consideration for therapeutic drug monitoring. 1, 2
Renal Impairment
- Levofloxacin: Reduce to three times weekly dosing when GFR <30 mL/min 1, 6
- Moxifloxacin: No dose adjustment needed 1, 6
- Aminoglycosides (amikacin, streptomycin): Reduce frequency to 2-3 times weekly to allow drug clearance 1
- Cycloserine: Start with 250 mg daily and verify with therapeutic drug monitoring 1
- Pyrazinamide: Reduce to three times weekly dosing 1
Hepatic Impairment
Standard doses can be used with frequent monitoring of liver function tests. 2 In patients with pre-existing liver disease but normal liver enzymes, all anti-tuberculosis drugs may be used with close monitoring. 7
Special Populations
Pregnancy: All first-line drugs (rifampin, isoniazid, ethambutol, pyrazinamide) can be used during pregnancy. Streptomycin should be avoided due to fetal ototoxicity. Add prophylactic pyridoxine 10-25 mg daily. 2, 4, 7
HIV Co-infection: Use standard short-course chemotherapy doses, but be aware of drug interactions with antiretroviral therapy, particularly rifampin with protease inhibitors and NNRTIs. Therapeutic drug monitoring may be necessary due to malabsorption risk. 2, 7
Diabetes Mellitus: Use standard regimen with strict glucose control. Doses of oral hypoglycemic agents may need to be increased due to rifampin interaction. Add prophylactic pyridoxine. 7
Common Pitfalls and Caveats
Pyridoxine supplementation (25-50 mg daily) should be given with isoniazid to all persons at risk of neuropathy, including pregnant women, breastfeeding infants, persons with HIV, patients with diabetes, alcoholism, malnutrition, chronic renal failure, or advanced age. 2
The fourth drug (ethambutol) in the initial phase can be omitted only when there is <4% primary isoniazid resistance in the community, no previous TB treatment, no exposure to drug-resistant cases, and the patient is not from a high-prevalence drug-resistant area. 1, 8 However, most experts recommend including ethambutol in all initial regimens due to difficulty in accurately assessing resistance risk. 1
For MDR-TB, at least four drugs to which the organism is likely susceptible must be used, with stepwise selection through the five drug groups based on efficacy, safety, and cost. 1, 9 Treatment of MDR-TB should be managed by physicians with specialized experience and access to quality-controlled drug susceptibility testing. 7
Fixed-dose combinations minimize the risk of selective drug intake and monotherapy, which can lead to acquired drug resistance. 7 All intermittent regimens (twice or thrice weekly) should be administered as directly observed therapy. 4, 8