Usual Adult Dose for Tuberculosis - Active

Once a day dosing: 15 to 30 mg/kg orally once a day

• Maximum dose: 2 grams/day

Intermittent dosing: 50 to 70 mg/kg orally 2 times a week

Duration of therapy: 2 months

Comments:

• This drug should only be used with other effective antituberculosis agents.
• Patients with HIV infection may require longer coursed of treatment.
• Dosing is based on lean body weight.

Uses:

• Initial treatment of active tuberculosis when combined with other antituberculosis agents
• After treatment failure with other primary drugs in any form of active tuberculosis

Infectious Diseases Society of America (IDSA), US Centers for Disease Control and Prevention (US CDC), and American Thoracic Society (ATS) Recommendations:
Daily dosing:

• Patients 40 to 55 kg: 1000 mg orally once a day
• Patients 56 to 75 kg: 1500 mg orally once a day
• Patients 76 to 90 kg: 2000 mg orally once a day

2 times a week dosing recommendations:

• Patients 40 to 55 kg: 2000 mg orally 2 times a week
• Patients 56 to 75 kg: 3000 mg orally 2 times a week
• Patients 76 to 90 kg: 4000 mg orally 2 times a week

3 times a week dosing recommendations:

• Patients 40 to 55 kg: 1500 mg orally 3 times a week
• Patients 56 to 75 kg: 2500 mg orally 3 times a week
• Patients 76 to 90 kg: 3000 mg orally 3 times a week

Use: First-line drug for the treatment of drug-susceptible tuberculosis

US Department of Health and Human Services (US HHS), National Institutes of Health (NIH), Health Resources and Services Administration (HRSA), and US CDC Recommendations:
DRUG-SUSCEPTIBLE TUBERCULOSIS:
Intensive phase: 5 mg/kg orally once a day PLUS rifampin/rifabutin, ethambutol, and pyrazinamide

• Duration of therapy: 2 months

Continuation phase: 5 mg/kg orally once a day for 5 to 7 days per week PLUS rifampin/rifabutin
Duration of therapy:

• Extrapulmonary in other sites: 6 months
• Pulmonary, drug susceptible: 6 months
• Extrapulmonary with bone/joint involvement: 6 to 9 months
• Pulmonary and positive culture at 2 months of treatment: 9 months
• Extrapulmonary with central nervous system involvement: 9 to 12 months

DRUG-RESISTANT TUBERCULOSIS:
Initial phase: 5 mg/kg orally once a day PLUS moxifloxacin/levofloxacin, ethambutol, rifampin/rifabutin, pyrazinamide, and an aminoglycoside/capreomycin

Weight-based dosing recommendations:
Patients 40 to 55 kg: 1000 mg orally once a day

• Patients 56 to 75 kg: 1500 mg orally once a day
• Patients 76 to 90 kg: 2000 mg orally once a day
• Patients greater than 90 kg: 2000 mg/day

Comments:

• If the organism is susceptible to this drug and rifampin, ethambutol may be discontinued during the intensive phase.
• Directly observed therapy (DOT) is recommended for patients with HIV-related tuberculosis.

Uses:

• Preferred treatment to prevent tuberculosis in patients with a positive screening test for latent tuberculosis infection, no evidence of active tuberculosis, and no prior history of treatment for active or latent tuberculosis
• Preferred treatment to prevent tuberculosis in patients with close contact with a person with infectious tuberculosis, regardless of a screening test result
• First-line drug for the treatment of active tuberculosis caused by Mycobacterium tuberculosis

Usual Adult Dose for Tuberculosis - Latent

Once a day dosing: 15 to 30 mg/kg orally once a day

• Maximum dose: 2 grams/day

Intermittent dosing: 50 to 70 mg/kg orally 2 times a week

Duration of therapy: 2 months

Comments:

• This drug should only be used with other effective antituberculosis agents.
• Patients with HIV infection may require longer coursed of treatment.
• Dosing is based on lean body weight.

Uses:

• Initial treatment of active tuberculosis when combined with other antituberculosis agents
• After treatment failure with other primary drugs in any form of active tuberculosis

Infectious Diseases Society of America (IDSA), US Centers for Disease Control and Prevention (US CDC), and American Thoracic Society (ATS) Recommendations:
Daily dosing:

• Patients 40 to 55 kg: 1000 mg orally once a day
• Patients 56 to 75 kg: 1500 mg orally once a day
• Patients 76 to 90 kg: 2000 mg orally once a day

2 times a week dosing recommendations:

• Patients 40 to 55 kg: 2000 mg orally 2 times a week
• Patients 56 to 75 kg: 3000 mg orally 2 times a week
• Patients 76 to 90 kg: 4000 mg orally 2 times a week

3 times a week dosing recommendations:

• Patients 40 to 55 kg: 1500 mg orally 3 times a week
• Patients 56 to 75 kg: 2500 mg orally 3 times a week
• Patients 76 to 90 kg: 3000 mg orally 3 times a week

Use: First-line drug for the treatment of drug-susceptible tuberculosis

US Department of Health and Human Services (US HHS), National Institutes of Health (NIH), Health Resources and Services Administration (HRSA), and US CDC Recommendations:
DRUG-SUSCEPTIBLE TUBERCULOSIS:
Intensive phase: 5 mg/kg orally once a day PLUS rifampin/rifabutin, ethambutol, and pyrazinamide

• Duration of therapy: 2 months

Continuation phase: 5 mg/kg orally once a day for 5 to 7 days per week PLUS rifampin/rifabutin
Duration of therapy:

• Extrapulmonary in other sites: 6 months
• Pulmonary, drug susceptible: 6 months
• Extrapulmonary with bone/joint involvement: 6 to 9 months
• Pulmonary and positive culture at 2 months of treatment: 9 months
• Extrapulmonary with central nervous system involvement: 9 to 12 months

DRUG-RESISTANT TUBERCULOSIS:
Initial phase: 5 mg/kg orally once a day PLUS moxifloxacin/levofloxacin, ethambutol, rifampin/rifabutin, pyrazinamide, and an aminoglycoside/capreomycin

Weight-based dosing recommendations:
Patients 40 to 55 kg: 1000 mg orally once a day

• Patients 56 to 75 kg: 1500 mg orally once a day
• Patients 76 to 90 kg: 2000 mg orally once a day
• Patients greater than 90 kg: 2000 mg/day

Comments:

• If the organism is susceptible to this drug and rifampin, ethambutol may be discontinued during the intensive phase.
• Directly observed therapy (DOT) is recommended for patients with HIV-related tuberculosis.

Uses:

• Preferred treatment to prevent tuberculosis in patients with a positive screening test for latent tuberculosis infection, no evidence of active tuberculosis, and no prior history of treatment for active or latent tuberculosis
• Preferred treatment to prevent tuberculosis in patients with close contact with a person with infectious tuberculosis, regardless of a screening test result
• First-line drug for the treatment of active tuberculosis caused by Mycobacterium tuberculosis

Usual Pediatric Dose for Tuberculosis - Extrapulmonary

Children:
Once a day dosing: 15 to 30 mg/kg orally once a day

• Maximum dose: 2 grams/day

Intermittent dosing: 50 to 70 mg/kg orally 2 times a week

Duration of therapy: 2 months

Comments:

• This drug should only be used with other effective antituberculosis agents.
• Patients with HIV infection may require longer coursed of treatment.
• Dosing is based on lean body weight.

Uses:

• Initial treatment of active tuberculosis when combined with other antituberculosis agents
• After treatment failure with other primary drugs in any form of active tuberculosis

US HHS, NIH, HRSA, and US CDC Recommendations:
DRUG-SUSCEPTIBLE TUBERCULOSIS:
Children:
Intensive phase: 30 to 40 mg/kg orally once a day PLUS isoniazid, rifampin, and ethambutol
Maximum dose: 2 grams/day
Duration of therapy: 2 months

Comment: Lymph node tuberculosis may be treated as minimal intrathoracic disease.

Use: First-line drug for the treatment of intrathoracic tuberculosis caused by susceptible strains of M tuberculosis

American Academy of Pediatrics (AAP) Recommendations:
Infants, Children, and Adolescents: 30 to 40 mg/kg orally once a day OR 50 mg/kg orally 2 times a week
Maximum dose: 2 grams/dose
Duration of therapy: 2 months

Uses:

• First-line drug for the treatment of drug-susceptible tuberculosis
• Treatment of pulmonary and extrapulmonary M tuberculosis infection (except meningitis)

Usual Pediatric Dose for Tuberculosis - Active

Children:
Once a day dosing: 15 to 30 mg/kg orally once a day

• Maximum dose: 2 grams/day

Intermittent dosing: 50 to 70 mg/kg orally 2 times a week

Duration of therapy: 2 months

Comments:

• This drug should only be used with other effective antituberculosis agents.
• Patients with HIV infection may require longer coursed of treatment.
• Dosing is based on lean body weight.

Uses:

• Initial treatment of active tuberculosis when combined with other antituberculosis agents
• After treatment failure with other primary drugs in any form of active tuberculosis

US HHS, NIH, HRSA, and US CDC Recommendations:
DRUG-SUSCEPTIBLE TUBERCULOSIS:
Children:
Intensive phase: 30 to 40 mg/kg orally once a day PLUS isoniazid, rifampin, and ethambutol
Maximum dose: 2 grams/day
Duration of therapy: 2 months

Comment: Lymph node tuberculosis may be treated as minimal intrathoracic disease.

Use: First-line drug for the treatment of intrathoracic tuberculosis caused by susceptible strains of M tuberculosis

American Academy of Pediatrics (AAP) Recommendations:
Infants, Children, and Adolescents: 30 to 40 mg/kg orally once a day OR 50 mg/kg orally 2 times a week
Maximum dose: 2 grams/dose
Duration of therapy: 2 months

Uses:

• First-line drug for the treatment of drug-susceptible tuberculosis
• Treatment of pulmonary and extrapulmonary M tuberculosis infection (except meningitis)

Renal Dose Adjustments

Dose adjustment(s) may be required; however, no specific guidelines have been suggested. Frequent monitoring recommended.

ATS, US CDC, and IDSA Recommendations:
CrCl less than 30 mL/min: 25 to 35 mg/kg orally 3 times a week

Liver Dose Adjustments

Mild to moderate liver dysfunction: Frequent monitoring recommended.
Severe liver damage/dysfunction: Contraindicated

During treatment:
Signs/symptoms of hepatocellular damage: Discontinue this drug and do not resume treatment.

Dose Adjustments

During treatment:
Signs/symptoms of hyperuricemia with acute gouty arthritis: Discontinue this drug and do not resume treatment.

Precautions

CONTRAINDICATIONS:

• Hypersensitivity to the active component or any of the ingredients
• Patients with acute gout
• Severe hepatic damage

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

ATS, US CDC, and IDSA Recommendations:
Hemodialysis: 25 to 35 mg/kg orally 3 times a week
Peritoneal dialysis: Data not available

Other Comments

Storage requirements:

• Protect from light.

Monitoring:

• Hepatic: Liver function tests (e.g., ALT, AST) at baseline, periodically every 2 to 4 weeks, and as clinically necessary thereafter
• Metabolic: Uric acid levels at baseline, periodically, and as clinically necessary thereafter

Patient advice:

• Advise patients to speak to their healthcare provider if they become pregnant, intend to become pregnant, or are breastfeeding.
• Patients should be instructed to complete the full course of therapy, and the importance of not missing any doses should be stressed.