What are the recommended dosing regimens for drug‑susceptible pulmonary tuberculosis in adults (including pregnant women), children, and for patients with hepatic impairment or multidrug‑resistant disease?

Tuberculosis Drug Dosing

Drug-Susceptible TB: Standard First-Line Regimen

For adults with drug-susceptible pulmonary TB, use a 2-month intensive phase of isoniazid 5 mg/kg daily (max 300 mg), rifampin 10 mg/kg daily (max 600 mg), pyrazinamide 15-30 mg/kg daily (max 2000 mg), and ethambutol 15-25 mg/kg daily (max 2500 mg), followed by a 4-month continuation phase of isoniazid and rifampin at the same doses. 1, 2

Adults: Daily Dosing

• Isoniazid: 5 mg/kg daily (maximum 300 mg) 1, 2
• Rifampin: 10 mg/kg daily (maximum 600 mg) 1, 2
• Pyrazinamide: 15-30 mg/kg daily (maximum 2000 mg) 1, 2
• Ethambutol: 15-25 mg/kg daily (maximum 2500 mg) 1, 2

Adults: Intermittent Dosing (Thrice-Weekly)

• Isoniazid: Same as daily dosing 3
• Rifampin: Same as daily dosing 3
• Pyrazinamide: 35 mg/kg (range 30-40 mg/kg) 2
• Ethambutol: 30 mg/kg (range 25-35 mg/kg) 2

Pediatric Dosing (Daily)

• Isoniazid: 10-15 mg/kg daily (maximum 300 mg) 1, 2
• Rifampin: 10-20 mg/kg daily (maximum 600 mg) 1, 2
• Pyrazinamide: 30-40 mg/kg daily (maximum 2000 mg) 1, 2
• Ethambutol: 15-25 mg/kg daily (maximum 2500 mg) 1, 2

Adolescents: Dosing Algorithm

Use adult doses if the adolescent is ≥15 years old OR weighs ≥40 kg; otherwise use pediatric weight-based dosing. 2

• For adolescents ≥15 years OR ≥40 kg: Use adult doses listed above 2
• For adolescents 12-14 years AND <40 kg: Use pediatric doses listed above 2

Special Populations

Pregnant Women

All first-line drugs (isoniazid, rifampin, pyrazinamide, ethambutol) can be safely used during pregnancy at standard doses, with mandatory pyridoxine 10-25 mg daily supplementation. 1, 4

• Use the same standard 6-month regimen as non-pregnant adults 4
• Avoid streptomycin due to fetal ototoxicity 4
• Pyridoxine (vitamin B6) 10-25 mg daily is mandatory to prevent peripheral neuropathy 1, 4

Hepatic Impairment

In patients with stable pre-existing liver disease but normal liver enzymes, use standard doses of all first-line drugs with frequent monitoring of liver function tests. 4

• Standard doses can be used with close monitoring 1
• Check liver function tests frequently, particularly in the first 2 weeks 5
• If hepatotoxicity develops, consider alternative regimens based on severity 4

Renal Impairment

Adjust doses of ethambutol, streptomycin, and isoniazid based on creatinine clearance; rifampin and pyrazinamide do not require adjustment. 4

• Ethambutol: Reduce to 15 mg/kg three times weekly when GFR <30 mL/min 5
• Streptomycin: Requires dose adjustment based on creatinine clearance 4
• Isoniazid: May require adjustment in severe renal failure 4
• Rifampin and pyrazinamide: No adjustment needed 4

Older Adults

Use standard adult doses in older adults with mandatory pyridoxine 25-50 mg daily supplementation due to increased risk of peripheral neuropathy. 5

• Same doses as younger adults: isoniazid 5 mg/kg (typically 300 mg), rifampin 10 mg/kg (typically 600 mg) 5
• Pyridoxine 25-50 mg daily is mandatory 5
• Adjust ethambutol to 15 mg/kg three times weekly if decreased renal function 5
• Monitor liver function frequently, especially in first 2 weeks 5

Obese Patients

For obese patients (>20% above ideal body weight), use ideal body weight or modified ideal body weight for initial dosing rather than actual body weight. 3, 2

• Modified ideal body weight formula: IBW + [0.40 × (actual weight – IBW)] 3
• Consider therapeutic drug monitoring in obese patients 3

Multidrug-Resistant TB: Second-Line Agents

Fluoroquinolones

• Levofloxacin (adults): 750-1000 mg daily; reduce to three times weekly when GFR <30 mL/min 1
• Levofloxacin (children): 15-20 mg/kg daily 1
• Moxifloxacin (adults): 400 mg daily; no adjustment needed for renal impairment 3, 1
• Moxifloxacin (children): 10-15 mg/kg daily (aim for serum concentrations of 3-5 μg/mL 2 hours post-dose) 3, 1

Injectable Agents

• Amikacin/Kanamycin/Capreomycin (adults): 15 mg/kg daily (some prefer 25 mg/kg three times weekly) 2
• Amikacin/Kanamycin/Capreomycin (children): 15-20 mg/kg daily 2

Oral Second-Line Agents

• Cycloserine (adults): 10-15 mg/kg total daily (usually 250-500 mg once or twice daily) 2
• Ethionamide (adults): 15-20 mg/kg total daily (usually 250-500 mg once or twice daily) 2
• Para-aminosalicylic acid (adults): 8-12 g total daily (usually 4000 mg 2-3 times daily) 2
• Para-aminosalicylic acid (children): 200-300 mg/kg total daily (divided 2-3 times daily) 2
• Bedaquiline (adults and children >12 years and >30 kg): 400 mg daily for 14 days, then 200 mg three times weekly 1

Critical Dosing Considerations

Pyridoxine Supplementation

Give pyridoxine 25-50 mg daily to all patients at risk of neuropathy, including pregnant women, breastfeeding infants, HIV-positive patients, diabetics, alcoholics, malnourished patients, those with chronic renal failure, and older adults. 2, 5, 4

Treatment Duration

• Standard drug-susceptible TB: 6 months total (2-month intensive phase + 4-month continuation phase) 3, 5
• Cavitary disease with positive culture at 2 months: Extend continuation phase to 7 months 3
• TB meningitis/CNS TB: 12 months total 5

HIV Co-infection

Use standard short-course chemotherapy doses in HIV co-infected patients, with awareness of drug interactions between rifampin and protease inhibitors/NNRTIs. 1, 4

• Standard doses are appropriate 1, 4
• Rifampin induces metabolism of protease inhibitors and reduces efficacy 4
• Consider therapeutic drug monitoring due to malabsorption risk 2
• Monitor closely for paradoxical reactions (immune reconstitution inflammatory syndrome) 4

Common Pitfalls to Avoid

• Do not use actual body weight for obese patients—this leads to overdosing; use ideal or modified ideal body weight instead 3, 2
• Do not forget pyridoxine in high-risk groups—peripheral neuropathy is preventable 2, 5
• Do not use streptomycin in pregnancy—it causes fetal ototoxicity 4
• Do not assume adolescent dosing is always adult dosing—the cutoff is ≥15 years OR ≥40 kg, whichever comes first 2
• Do not use rifampin with protease inhibitors without dose adjustment—rifampin significantly reduces antiretroviral efficacy 4