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First-line antituberculosis drugs for treatment of CNS tuberculosis

First-line antituberculosis drugs for treatment of CNS tuberculosis
Drug Adult dose* Pediatric dose
IsoniazidΔ 5 mg/kg (usual maximum dose 300 mg) 10 to 15 mg/kg per day
Rifampin (rifampicin) 10 mg/kg (usual maximum dose 600 mg) 20 to 30 mg/kg per day
Rifabutin 5 mg/kg (usual maximum dose 300 mg) --
Pyrazinamide§ Patient weight 40 to 55 kg¥:
  • 1000 mg (18.2 to 25 mg/kg)
30 to 40 mg/kg per day
Patient weight 56 to 75 kg¥:
  • 1500 mg (20 to 26.8 mg/kg)
 
Patient weight 76 to 90 kg¥:
  • 2000 mg (22.2 to 26.3 mg/kg)
 
Ethambutol** Patient weight 40 to 55 kg¥:
  • 800 mg (14.5 to 20 mg/kg)
15 to 25 mg/kg per day
Patient weight 56 to 75 kg¥:
  • 1200 mg (16 to 21.4 mg/kg)
 
Patient weight 76 to 90 kg¥:
  • 1600 mg (17.8 to 21.1 mg/kg)
 
Ethionamide -- 15 to 20 mg/kg per day in 2 or 3 divided doses
Amikacin -- 15 to 20 mg/kg per day
Levofloxacin   15 to 20 mg/kg per day
Antituberculous agents are used in multidrug combination regimens of varying duration, which are described in detail in a separate table (refer to the UpToDate table on regimens for treatment of drug-susceptible tuberculosis) and in the accompanying text.

CNS: central nervous system.

* Adult dosing listed in this table is used in patients ≥15 years old or >40 kg. Dosing based on actual weight is acceptable in patients who are not obese. For obese patients (>20% above ideal body weight [IBW]), dosing based on IBW may be preferred for initial doses. Some clinicians prefer a modified IBW (IBW + [0.40 × (actual weight − IBW)]) as is done for initial aminoglycoside doses. Because tuberculosis drug dosing for obese patients has not been established, therapeutic drug monitoring may be considered for such patients.

¶ For empiric treatment of CNS TB (not known or suspected to be drug resistant) in children, we are in agreement with the American Academy of Pediatrics, which recommends treatment with an intensive phase 4-drug regimen consisting of isoniazid, rifampin, pyrazinamide, and ethionamide or levofloxacin (in place of ethambutol, given its poor CNS penetration) administered daily for 2 months.

Δ Pyridoxine (vitamin B6; 25 to 50 mg/day) is given with isoniazid to individuals at risk for neuropathy (eg, pregnant women, breastfeeding infants, and individuals with HIV infection, diabetes, alcoholism, malnutrition, chronic renal failure, or advanced age). For patients with peripheral neuropathy, experts recommend increasing pyridoxine dose to 100 mg/day.

◊ Rifabutin dose may need to be adjusted when there is concomitant use of protease inhibitors or nonnucleoside reverse transcriptase inhibitors. Refer to the UpToDate topic on treatment of pulmonary tuberculosis in HIV-infected adults for specific dose adjustments.

§ For patients with creatinine clearance <30 mL/min (by Cockroft-Gault equation) or for patients receiving intermittent hemodialysis, pyrazinamide dosing consists of 25 to 35 mg/kg (ideal body weight) per dose orally 3 times per week (not daily); max 2.5 g per dose. On the day of hemodialysis, medications should be administered after hemodialysis. Monitoring of serum drug concentrations should be considered to ensure adequate drug absorption without excessive accumulation and to assist in avoiding toxicity.

¥ Based on estimated lean body weight.

‡ Patients >90 kg should have serum concentration monitoring. In obese patients, weight-based dosing is likely best based on measurements of ideal (versus total) body weight.

† Maximum dose regardless of weight.

** For patients with creatinine clearance <30 mL/min (by Cockroft-Gault equation) or for patients receiving intermittent hemodialysis, ethambutol dosing consists of 20 to 25 mg/kg (ideal body weight) per dose orally 3 times per week (not daily); max 1.6 g per dose. On the day of hemodialysis, medications should be administered after hemodialysis. Monitoring of serum drug concentrations should be considered to ensure adequate drug absorption without excessive accumulation and to assist in avoiding toxicity.
Data adapted from:
  1. Nahid P, Dorman SE, Alipanah N, et al. Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of American clinical practice guidelines: Treatment of drug-susceptible tuberculosis. Clin Infect Dis 2016; 63:e147.
  2. Curry International Tuberculosis Center and California Department of Public Health, 2016: Drug-Resistant Tuberculosis: A Survival Guide for Clinicians, Third Edition.
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