Drug Detail:Isoniazid (Isoniazid [ eye-so-nye-a-zid ])
Drug Class: Hydrazide derivatives
Usual Adult Dose for Tuberculosis - Extrapulmonary
Pulmonary Tuberculosis without HIV Infection:
OPTION 1:
Initial regimen: 5 mg/kg orally once a day (maximum 300 mg/day) PLUS rifampin, pyrazinamide, and ethambutol/streptomycin
- Duration of therapy: 8 weeks
Continuation regimen: 5 mg/kg orally once a day (maximum 300 mg/day) OR 15 mg/kg orally 2 to 3 times a week (maximum 900 mg/day) PLUS rifampin
- Duration of therapy: 16 weeks
OPTION 2:
Initial regimen: 5 mg/kg orally once a day (maximum 300 mg/day) PLUS rifampin, pyrazinamide, and streptomycin/ethambutol
- Duration of therapy: 2 weeks
Followed by: 15 mg/kg orally 2 times a week (maximum 900 mg/day) PLUS rifampin, pyrazinamide, and streptomycin/ethambutol
- Duration of therapy: 6 weeks
Continuation regimen: 15 mg/kg orally 2 times a week (maximum 900 mg/day) PLUS rifampin
- Duration of therapy: 16 weeks
OPTION 3:
15 mg/kg orally 3 times a week (maximum 900 mg/day) PLUS rifampin, pyrazinamide, and streptomycin/ethambutol
- Duration of therapy: 6 months
Extrapulmonary Tuberculosis:
Daily dosing: 5 mg/kg orally once a day
- Maximum dose: 300 mg/day
Intermittent dosing: 15 mg/kg orally 2 to 3 times a week
- Maximum dose: 900 mg/day
Duration of therapy:
- Extrapulmonary tuberculosis: 6 to 9 months
- Bone/joint tuberculosis: 12 months
- Miliary tuberculosis: 12 months
Comments:
- Doses given 2 or 3 times a week should be given via directly observed therapy (DOT).
- Adjunctive treatment (e.g., surgery, corticosteroids) may be necessary in patients with extrapulmonary tuberculosis.
- IM formulations may be used when oral administration is not possible.
Use: Treatment for all forms of susceptible tuberculosis
American Thoracic Society (ATS), US Centers for Disease Control and Prevention (US CDC), and Infectious Diseases Society of America (IDSA) Recommendations:
Up to 40 kg:
- Daily regimen: 10 to 15 mg/kg IM, IV, or orally once a day
- Intermittent regimen: 20 to 30 mg IM, IV, or orally 2 to 3 times a week
Over 40 kg:
- Daily regimen: 5 mg/kg (usually 300 mg/day) IM, IV, or orally once a day
- Intermittent regimen: 15 mg/kg (up to 900 mg/dose) IM, IV, or orally 2 to 3 times a week
Comment: Pyridoxine 25 to 50 mg/day should be considered in all patients at risk of developing neuropathy; patients with peripheral neuropathy may be given 100 mg/day.
Use: 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:
LATENT TUBERCULOSIS:
Preferred therapy: 300 mg orally once a day OR 900 mg orally 2 times a week
- Duration of therapy: 9 months
Alternative therapy: 15 mg/kg orally once a week PLUS rifapentine
- Duration of therapy: 12 weeks
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
Comments:
- Pyridoxine 25 to 50 mg orally should be given to patients during treatment for latent tuberculosis.
- If the organism is susceptible to this drug and rifampin, ethambutol may be discontinued during the intensive phase.
- 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 - Active
Pulmonary Tuberculosis without HIV Infection:
OPTION 1:
Initial regimen: 5 mg/kg orally once a day (maximum 300 mg/day) PLUS rifampin, pyrazinamide, and ethambutol/streptomycin
- Duration of therapy: 8 weeks
Continuation regimen: 5 mg/kg orally once a day (maximum 300 mg/day) OR 15 mg/kg orally 2 to 3 times a week (maximum 900 mg/day) PLUS rifampin
- Duration of therapy: 16 weeks
OPTION 2:
Initial regimen: 5 mg/kg orally once a day (maximum 300 mg/day) PLUS rifampin, pyrazinamide, and streptomycin/ethambutol
- Duration of therapy: 2 weeks
Followed by: 15 mg/kg orally 2 times a week (maximum 900 mg/day) PLUS rifampin, pyrazinamide, and streptomycin/ethambutol
- Duration of therapy: 6 weeks
Continuation regimen: 15 mg/kg orally 2 times a week (maximum 900 mg/day) PLUS rifampin
- Duration of therapy: 16 weeks
OPTION 3:
15 mg/kg orally 3 times a week (maximum 900 mg/day) PLUS rifampin, pyrazinamide, and streptomycin/ethambutol
- Duration of therapy: 6 months
Extrapulmonary Tuberculosis:
Daily dosing: 5 mg/kg orally once a day
- Maximum dose: 300 mg/day
Intermittent dosing: 15 mg/kg orally 2 to 3 times a week
- Maximum dose: 900 mg/day
Duration of therapy:
- Extrapulmonary tuberculosis: 6 to 9 months
- Bone/joint tuberculosis: 12 months
- Miliary tuberculosis: 12 months
Comments:
- Doses given 2 or 3 times a week should be given via directly observed therapy (DOT).
- Adjunctive treatment (e.g., surgery, corticosteroids) may be necessary in patients with extrapulmonary tuberculosis.
- IM formulations may be used when oral administration is not possible.
Use: Treatment for all forms of susceptible tuberculosis
American Thoracic Society (ATS), US Centers for Disease Control and Prevention (US CDC), and Infectious Diseases Society of America (IDSA) Recommendations:
Up to 40 kg:
- Daily regimen: 10 to 15 mg/kg IM, IV, or orally once a day
- Intermittent regimen: 20 to 30 mg IM, IV, or orally 2 to 3 times a week
Over 40 kg:
- Daily regimen: 5 mg/kg (usually 300 mg/day) IM, IV, or orally once a day
- Intermittent regimen: 15 mg/kg (up to 900 mg/dose) IM, IV, or orally 2 to 3 times a week
Comment: Pyridoxine 25 to 50 mg/day should be considered in all patients at risk of developing neuropathy; patients with peripheral neuropathy may be given 100 mg/day.
Use: 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:
LATENT TUBERCULOSIS:
Preferred therapy: 300 mg orally once a day OR 900 mg orally 2 times a week
- Duration of therapy: 9 months
Alternative therapy: 15 mg/kg orally once a week PLUS rifapentine
- Duration of therapy: 12 weeks
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
Comments:
- Pyridoxine 25 to 50 mg orally should be given to patients during treatment for latent tuberculosis.
- If the organism is susceptible to this drug and rifampin, ethambutol may be discontinued during the intensive phase.
- 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
Pulmonary Tuberculosis without HIV Infection:
OPTION 1:
Initial regimen: 5 mg/kg orally once a day (maximum 300 mg/day) PLUS rifampin, pyrazinamide, and ethambutol/streptomycin
- Duration of therapy: 8 weeks
Continuation regimen: 5 mg/kg orally once a day (maximum 300 mg/day) OR 15 mg/kg orally 2 to 3 times a week (maximum 900 mg/day) PLUS rifampin
- Duration of therapy: 16 weeks
OPTION 2:
Initial regimen: 5 mg/kg orally once a day (maximum 300 mg/day) PLUS rifampin, pyrazinamide, and streptomycin/ethambutol
- Duration of therapy: 2 weeks
Followed by: 15 mg/kg orally 2 times a week (maximum 900 mg/day) PLUS rifampin, pyrazinamide, and streptomycin/ethambutol
- Duration of therapy: 6 weeks
Continuation regimen: 15 mg/kg orally 2 times a week (maximum 900 mg/day) PLUS rifampin
- Duration of therapy: 16 weeks
OPTION 3:
15 mg/kg orally 3 times a week (maximum 900 mg/day) PLUS rifampin, pyrazinamide, and streptomycin/ethambutol
- Duration of therapy: 6 months
Extrapulmonary Tuberculosis:
Daily dosing: 5 mg/kg orally once a day
- Maximum dose: 300 mg/day
Intermittent dosing: 15 mg/kg orally 2 to 3 times a week
- Maximum dose: 900 mg/day
Duration of therapy:
- Extrapulmonary tuberculosis: 6 to 9 months
- Bone/joint tuberculosis: 12 months
- Miliary tuberculosis: 12 months
Comments:
- Doses given 2 or 3 times a week should be given via directly observed therapy (DOT).
- Adjunctive treatment (e.g., surgery, corticosteroids) may be necessary in patients with extrapulmonary tuberculosis.
- IM formulations may be used when oral administration is not possible.
Use: Treatment for all forms of susceptible tuberculosis
American Thoracic Society (ATS), US Centers for Disease Control and Prevention (US CDC), and Infectious Diseases Society of America (IDSA) Recommendations:
Up to 40 kg:
- Daily regimen: 10 to 15 mg/kg IM, IV, or orally once a day
- Intermittent regimen: 20 to 30 mg IM, IV, or orally 2 to 3 times a week
Over 40 kg:
- Daily regimen: 5 mg/kg (usually 300 mg/day) IM, IV, or orally once a day
- Intermittent regimen: 15 mg/kg (up to 900 mg/dose) IM, IV, or orally 2 to 3 times a week
Comment: Pyridoxine 25 to 50 mg/day should be considered in all patients at risk of developing neuropathy; patients with peripheral neuropathy may be given 100 mg/day.
Use: 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:
LATENT TUBERCULOSIS:
Preferred therapy: 300 mg orally once a day OR 900 mg orally 2 times a week
- Duration of therapy: 9 months
Alternative therapy: 15 mg/kg orally once a week PLUS rifapentine
- Duration of therapy: 12 weeks
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
Comments:
- Pyridoxine 25 to 50 mg orally should be given to patients during treatment for latent tuberculosis.
- If the organism is susceptible to this drug and rifampin, ethambutol may be discontinued during the intensive phase.
- 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 - Prophylaxis
Adults over 30 kg: 300 mg orally once a day
Duration of therapy:
- Close contact with newly diagnosed tuberculosis patients: At least 12 weeks
- Fibrotic pulmonary lesions or pulmonary silicosis: 12 months (or 4 months PLUS rifampin)
- Patients with HIV: At least 12 months
Comments:
- Bacteriologically positive or radiographically progressive tuberculosis should be excluded before starting treatment.
- Pyridoxine is recommended in patients who are malnourished and those at risk of neuropathy (e.g., alcoholics, patients with diabetes).
- IM formulations may be used when oral administration is not possible.
Uses:
Preventive therapy in:
- Close contacts of persons with newly diagnosed infectious tuberculosis
- IV drug users known to be HIV-seronegative
- Patients with HIV infection and persons with risk factors for HIV infection whose status is unknown, but who are suspected of having HIV infection
- Patients with the following medical conditions: clinical situations associated with substantial rapid weight loss/chronic undernutrition (e.g., carcinomas of the upper oropharynx and upper gastrointestinal tract that prevent adequate nutritional intake, chronic malabsorption syndromes, chronic peptic ulcer disease, intestinal bypass surgery, postgastrectomy state with/without weight loss), diabetes mellitus, end-stage renal disease, immunosuppressive therapy, prolonged adrenocorticosteroid therapy, silicosis, some hematologic and reticuloendothelial diseases (e.g., leukemia, Hodgkin's lymphoma)
- Patients younger than 35 years in high-incidence groups (e.g., foreign-born patients from high-prevalence countries who never received bacilli Calmette-Guerin [BCG] vaccine, medically underserved, low-income populations, including high-risk racial or ethnic minority populations, especially blacks, Hispanics, and Native Americans, and residents of facilities for long-term care [e.g., correctional institutions, nursing homes, mental institutions])
- Patients younger than 35 years with a tuberculin skin test reaction of 15 mm or more
- Persons with abnormal chest radiographs that show fibrotic lesions likely to represent old healed tuberculosis or pulmonary silicosis
- Recent converters (e.g., tuberculin skin test with 10 mm or greater (younger than 35 years) OR 15 mm or greater (35 years and older) within a 2-year period)
US HHS, NIH, HRSA, and US CDC Recommendations:
Preferred choice: 300 mg orally once a day OR 900 mg orally 2 times a week
- Duration of therapy: 9 months
Alternative choice: 900 mg orally once a week PLUS rifapentine
- Duration of therapy: 12 weeks
Comments:
- Patients receiving intermittent dosing should be given doses via DOT.
- Pyridoxine 25 to 50 mg orally once a day should be given with this drug.
Uses:
- Prophylaxis to prevent the first episode of tuberculosis in patients with a positive screening test for latent tuberculosis infection, with no evidence of active tuberculosis, and no prior treatment for active or latent tuberculosis
- Prophylaxis to prevent the first episode of tuberculosis in patients with close contact with a person with infectious tuberculosis, with no evidence of active tuberculosis, regardless of screening test results
Usual Adult Dose for Mycobacterium kansasii
ATS and IDSA Recommendations:
5 mg/kg orally once a day
Maximum dose: 300 mg/day
Duration of therapy: 18 months
Comment: Patients should have at least 12 months of negative sputum cultures.
Use: Treatment of Mycobacterium kansasii pulmonary disease
Usual Pediatric Dose for Tuberculosis - Extrapulmonary
PULMONARY TUBERCULOSIS WITHOUT HIV INFECTION:
Option 1:
Initial regimen: 10 to 15 mg/kg IM or orally once a day (maximum 300 mg/day) PLUS rifampin, pyrazinamide, and ethambutol/streptomycin
- Duration of therapy: 8 weeks
Continuation regimen: 10 to 15 mg/kg IM or orally once a day (maximum 300 mg/day) OR 20 to 40 mg/kg IM or orally 2 to 3 times a week (maximum 900 mg/day) PLUS rifampin
- Duration of therapy: 16 weeks
Option 2:
Initial regimen: 10 to 15 mg/kg IM or orally once a day (maximum 300 mg/day) PLUS rifampin, pyrazinamide, and streptomycin/ethambutol
- Duration of therapy: 2 weeks
Followed by: 20 to 40 mg/kg IM or orally 2 times a week (maximum 900 mg/day) PLUS rifampin, pyrazinamide, and streptomycin/ethambutol
- Duration of therapy: 6 weeks
Continuation regimen: 20 to 40 mg/kg IM or orally 2 times a week (maximum 900 mg/day) PLUS rifampin
- Duration of therapy: 16 weeks
Option 3:
20 to 40 mg/kg IM or orally 3 times a week (maximum 900 mg/day) PLUS rifampin, pyrazinamide, and streptomycin/ethambutol
- Duration of therapy: 6 months
EXTRAPULMONARY TUBERCULOSIS:
Daily dosing: 10 to 15 mg/kg IM or orally once a day
- Maximum dose: 300 mg/day
Intermittent dosing: 20 to 40 mg/kg IM or orally 2 to 3 times a week
- Maximum dose: 900 mg/day
Duration of therapy:
- Extrapulmonary tuberculosis: 6 to 9 months
- Bone/joint tuberculosis: 12 months
- Miliary tuberculosis: 12 months
Comments:
- Doses given 2 or 3 times a week should be given via DOT.
- Adjunctive treatment (e.g., surgery, corticosteroids) may be necessary in patients with extrapulmonary tuberculosis.
- IM formulations may be used when oral administration is not possible.
Use: Treatment for all forms of susceptible tuberculosis
American Academy of Pediatrics (AAP) Recommendations:
Infants, Children, and Adolescents:
Daily dosing: 10 to 15 mg/kg orally once a day
- Maximum dose: 300 mg/day
Intermittent dosing: 20 to 30 mg orally 2 times a week
- Maximum dose: 900 mg/dose
Duration of therapy:
- Latent tuberculosis (drug-susceptible): 9 months
- Pulmonary and extrapulmonary tuberculosis (except meningitis): 2 months (3-drug regimen), then 4 months for drug-susceptible M tuberculosis OR 9 to 12 months for drug-susceptible Mycobacterium bovis
- Meningitis: 2 months (4-drug regimen), followed by 7 to 10 months of this drug and rifampin (once a day or 2 times a week)
Comments:
- Daily treatment is preferred for latent tuberculosis; however, DOT may be used if daily treatment is not possible.
- Patients who receive a 3-drug regimen (e.g., this drug, rifampin, and pyrazinamide) should have a low risk of drug resistance.
- Patients with only hilar adenopathy and a low risk of drug resistance may receive treatment with this drug and rifampin for 6 months.
- Patients with meningitis caused by M bovis should receive treatment with this drug, rifampin, and an aminoglycoside or ethionamide for 2 months, followed by at least 7 to 10 months of this drug and rifampin.
Uses:
- Treatment of latent Mycobacterial tuberculosis infection (e.g., positive tuberculin skin tests or interferon-gamma release assay result, no disease)
- Treatment of pulmonary and extrapulmonary Mycobacterial tuberculosis infection (except meningitis) caused by M tuberculosis or M bovis
- Treatment of meningitis caused by M tuberculosis or M bovis
ATS, US CDC, and IDSA Recommendations:
Less than 15 years OR up to 40 kg:
- Daily regimen: 10 to 15 mg/kg IM, IV, or orally once a day
- Intermittent regimen: 20 to 30 mg IM, IV, or orally 2 to 3 times a week
15 years and older AND/OR over 40 kg:
- Daily regimen: 5 mg/kg (usually 300 mg/day) IM, IV, or orally once a day
- Intermittent regimen: 15 mg/kg (up to 900 mg/dose) IM, IV, or orally 2 to 3 times a week
Comment: Pyridoxine 25 to 50 mg/day should be considered in all patients at risk of developing neuropathy; patients with peripheral neuropathy may be given 100 mg/day.
Use: Treatment of drug-susceptible tuberculosis
US HHS, NIH, HRSA, and US CDC Recommendations:
Children:
DRUG-SUSCEPTIBLE TUBERCULOSIS:
Intensive Phase: 10 to 15 mg/kg orally once a day PLUS rifampin, pyrazinamide, and ethambutol
Maximum dose: 300 mg/day
Duration of therapy: 2 months
Continuation Phase: 10 to 15 mg/kg (up to 300 mg/day) orally once a day PLUS rifampin OR 20 to 30 mg/kg IM or orally 3 times a week
Duration of therapy:
- Bone/joint disease or meningitis: Up to 10 months
- Intrathoracic disease, lymph node tuberculosis: 7 months
- Minimal disease and in the absence of significant immune compromise: 4 months
Comment: The total duration of treatment is at least 12 months for minimal disease, and 18 to 24 months after non-bacteriological diagnosis or after culture conversion.
Uses:
- First-line drug for the treatment of active tuberculosis caused by M tuberculosis
- Alternative drug (as part of a 3-drug regimen) for the treatment of fully drug-susceptible tuberculosis in the absence of significant immune compromise
Usual Pediatric Dose for Tuberculosis - Active
PULMONARY TUBERCULOSIS WITHOUT HIV INFECTION:
Option 1:
Initial regimen: 10 to 15 mg/kg IM or orally once a day (maximum 300 mg/day) PLUS rifampin, pyrazinamide, and ethambutol/streptomycin
- Duration of therapy: 8 weeks
Continuation regimen: 10 to 15 mg/kg IM or orally once a day (maximum 300 mg/day) OR 20 to 40 mg/kg IM or orally 2 to 3 times a week (maximum 900 mg/day) PLUS rifampin
- Duration of therapy: 16 weeks
Option 2:
Initial regimen: 10 to 15 mg/kg IM or orally once a day (maximum 300 mg/day) PLUS rifampin, pyrazinamide, and streptomycin/ethambutol
- Duration of therapy: 2 weeks
Followed by: 20 to 40 mg/kg IM or orally 2 times a week (maximum 900 mg/day) PLUS rifampin, pyrazinamide, and streptomycin/ethambutol
- Duration of therapy: 6 weeks
Continuation regimen: 20 to 40 mg/kg IM or orally 2 times a week (maximum 900 mg/day) PLUS rifampin
- Duration of therapy: 16 weeks
Option 3:
20 to 40 mg/kg IM or orally 3 times a week (maximum 900 mg/day) PLUS rifampin, pyrazinamide, and streptomycin/ethambutol
- Duration of therapy: 6 months
EXTRAPULMONARY TUBERCULOSIS:
Daily dosing: 10 to 15 mg/kg IM or orally once a day
- Maximum dose: 300 mg/day
Intermittent dosing: 20 to 40 mg/kg IM or orally 2 to 3 times a week
- Maximum dose: 900 mg/day
Duration of therapy:
- Extrapulmonary tuberculosis: 6 to 9 months
- Bone/joint tuberculosis: 12 months
- Miliary tuberculosis: 12 months
Comments:
- Doses given 2 or 3 times a week should be given via DOT.
- Adjunctive treatment (e.g., surgery, corticosteroids) may be necessary in patients with extrapulmonary tuberculosis.
- IM formulations may be used when oral administration is not possible.
Use: Treatment for all forms of susceptible tuberculosis
American Academy of Pediatrics (AAP) Recommendations:
Infants, Children, and Adolescents:
Daily dosing: 10 to 15 mg/kg orally once a day
- Maximum dose: 300 mg/day
Intermittent dosing: 20 to 30 mg orally 2 times a week
- Maximum dose: 900 mg/dose
Duration of therapy:
- Latent tuberculosis (drug-susceptible): 9 months
- Pulmonary and extrapulmonary tuberculosis (except meningitis): 2 months (3-drug regimen), then 4 months for drug-susceptible M tuberculosis OR 9 to 12 months for drug-susceptible Mycobacterium bovis
- Meningitis: 2 months (4-drug regimen), followed by 7 to 10 months of this drug and rifampin (once a day or 2 times a week)
Comments:
- Daily treatment is preferred for latent tuberculosis; however, DOT may be used if daily treatment is not possible.
- Patients who receive a 3-drug regimen (e.g., this drug, rifampin, and pyrazinamide) should have a low risk of drug resistance.
- Patients with only hilar adenopathy and a low risk of drug resistance may receive treatment with this drug and rifampin for 6 months.
- Patients with meningitis caused by M bovis should receive treatment with this drug, rifampin, and an aminoglycoside or ethionamide for 2 months, followed by at least 7 to 10 months of this drug and rifampin.
Uses:
- Treatment of latent Mycobacterial tuberculosis infection (e.g., positive tuberculin skin tests or interferon-gamma release assay result, no disease)
- Treatment of pulmonary and extrapulmonary Mycobacterial tuberculosis infection (except meningitis) caused by M tuberculosis or M bovis
- Treatment of meningitis caused by M tuberculosis or M bovis
ATS, US CDC, and IDSA Recommendations:
Less than 15 years OR up to 40 kg:
- Daily regimen: 10 to 15 mg/kg IM, IV, or orally once a day
- Intermittent regimen: 20 to 30 mg IM, IV, or orally 2 to 3 times a week
15 years and older AND/OR over 40 kg:
- Daily regimen: 5 mg/kg (usually 300 mg/day) IM, IV, or orally once a day
- Intermittent regimen: 15 mg/kg (up to 900 mg/dose) IM, IV, or orally 2 to 3 times a week
Comment: Pyridoxine 25 to 50 mg/day should be considered in all patients at risk of developing neuropathy; patients with peripheral neuropathy may be given 100 mg/day.
Use: Treatment of drug-susceptible tuberculosis
US HHS, NIH, HRSA, and US CDC Recommendations:
Children:
DRUG-SUSCEPTIBLE TUBERCULOSIS:
Intensive Phase: 10 to 15 mg/kg orally once a day PLUS rifampin, pyrazinamide, and ethambutol
Maximum dose: 300 mg/day
Duration of therapy: 2 months
Continuation Phase: 10 to 15 mg/kg (up to 300 mg/day) orally once a day PLUS rifampin OR 20 to 30 mg/kg IM or orally 3 times a week
Duration of therapy:
- Bone/joint disease or meningitis: Up to 10 months
- Intrathoracic disease, lymph node tuberculosis: 7 months
- Minimal disease and in the absence of significant immune compromise: 4 months
Comment: The total duration of treatment is at least 12 months for minimal disease, and 18 to 24 months after non-bacteriological diagnosis or after culture conversion.
Uses:
- First-line drug for the treatment of active tuberculosis caused by M tuberculosis
- Alternative drug (as part of a 3-drug regimen) for the treatment of fully drug-susceptible tuberculosis in the absence of significant immune compromise
Usual Pediatric Dose for Tuberculosis - Latent
PULMONARY TUBERCULOSIS WITHOUT HIV INFECTION:
Option 1:
Initial regimen: 10 to 15 mg/kg IM or orally once a day (maximum 300 mg/day) PLUS rifampin, pyrazinamide, and ethambutol/streptomycin
- Duration of therapy: 8 weeks
Continuation regimen: 10 to 15 mg/kg IM or orally once a day (maximum 300 mg/day) OR 20 to 40 mg/kg IM or orally 2 to 3 times a week (maximum 900 mg/day) PLUS rifampin
- Duration of therapy: 16 weeks
Option 2:
Initial regimen: 10 to 15 mg/kg IM or orally once a day (maximum 300 mg/day) PLUS rifampin, pyrazinamide, and streptomycin/ethambutol
- Duration of therapy: 2 weeks
Followed by: 20 to 40 mg/kg IM or orally 2 times a week (maximum 900 mg/day) PLUS rifampin, pyrazinamide, and streptomycin/ethambutol
- Duration of therapy: 6 weeks
Continuation regimen: 20 to 40 mg/kg IM or orally 2 times a week (maximum 900 mg/day) PLUS rifampin
- Duration of therapy: 16 weeks
Option 3:
20 to 40 mg/kg IM or orally 3 times a week (maximum 900 mg/day) PLUS rifampin, pyrazinamide, and streptomycin/ethambutol
- Duration of therapy: 6 months
EXTRAPULMONARY TUBERCULOSIS:
Daily dosing: 10 to 15 mg/kg IM or orally once a day
- Maximum dose: 300 mg/day
Intermittent dosing: 20 to 40 mg/kg IM or orally 2 to 3 times a week
- Maximum dose: 900 mg/day
Duration of therapy:
- Extrapulmonary tuberculosis: 6 to 9 months
- Bone/joint tuberculosis: 12 months
- Miliary tuberculosis: 12 months
Comments:
- Doses given 2 or 3 times a week should be given via DOT.
- Adjunctive treatment (e.g., surgery, corticosteroids) may be necessary in patients with extrapulmonary tuberculosis.
- IM formulations may be used when oral administration is not possible.
Use: Treatment for all forms of susceptible tuberculosis
American Academy of Pediatrics (AAP) Recommendations:
Infants, Children, and Adolescents:
Daily dosing: 10 to 15 mg/kg orally once a day
- Maximum dose: 300 mg/day
Intermittent dosing: 20 to 30 mg orally 2 times a week
- Maximum dose: 900 mg/dose
Duration of therapy:
- Latent tuberculosis (drug-susceptible): 9 months
- Pulmonary and extrapulmonary tuberculosis (except meningitis): 2 months (3-drug regimen), then 4 months for drug-susceptible M tuberculosis OR 9 to 12 months for drug-susceptible Mycobacterium bovis
- Meningitis: 2 months (4-drug regimen), followed by 7 to 10 months of this drug and rifampin (once a day or 2 times a week)
Comments:
- Daily treatment is preferred for latent tuberculosis; however, DOT may be used if daily treatment is not possible.
- Patients who receive a 3-drug regimen (e.g., this drug, rifampin, and pyrazinamide) should have a low risk of drug resistance.
- Patients with only hilar adenopathy and a low risk of drug resistance may receive treatment with this drug and rifampin for 6 months.
- Patients with meningitis caused by M bovis should receive treatment with this drug, rifampin, and an aminoglycoside or ethionamide for 2 months, followed by at least 7 to 10 months of this drug and rifampin.
Uses:
- Treatment of latent Mycobacterial tuberculosis infection (e.g., positive tuberculin skin tests or interferon-gamma release assay result, no disease)
- Treatment of pulmonary and extrapulmonary Mycobacterial tuberculosis infection (except meningitis) caused by M tuberculosis or M bovis
- Treatment of meningitis caused by M tuberculosis or M bovis
ATS, US CDC, and IDSA Recommendations:
Less than 15 years OR up to 40 kg:
- Daily regimen: 10 to 15 mg/kg IM, IV, or orally once a day
- Intermittent regimen: 20 to 30 mg IM, IV, or orally 2 to 3 times a week
15 years and older AND/OR over 40 kg:
- Daily regimen: 5 mg/kg (usually 300 mg/day) IM, IV, or orally once a day
- Intermittent regimen: 15 mg/kg (up to 900 mg/dose) IM, IV, or orally 2 to 3 times a week
Comment: Pyridoxine 25 to 50 mg/day should be considered in all patients at risk of developing neuropathy; patients with peripheral neuropathy may be given 100 mg/day.
Use: Treatment of drug-susceptible tuberculosis
US HHS, NIH, HRSA, and US CDC Recommendations:
Children:
DRUG-SUSCEPTIBLE TUBERCULOSIS:
Intensive Phase: 10 to 15 mg/kg orally once a day PLUS rifampin, pyrazinamide, and ethambutol
Maximum dose: 300 mg/day
Duration of therapy: 2 months
Continuation Phase: 10 to 15 mg/kg (up to 300 mg/day) orally once a day PLUS rifampin OR 20 to 30 mg/kg IM or orally 3 times a week
Duration of therapy:
- Bone/joint disease or meningitis: Up to 10 months
- Intrathoracic disease, lymph node tuberculosis: 7 months
- Minimal disease and in the absence of significant immune compromise: 4 months
Comment: The total duration of treatment is at least 12 months for minimal disease, and 18 to 24 months after non-bacteriological diagnosis or after culture conversion.
Uses:
- First-line drug for the treatment of active tuberculosis caused by M tuberculosis
- Alternative drug (as part of a 3-drug regimen) for the treatment of fully drug-susceptible tuberculosis in the absence of significant immune compromise
Usual Pediatric Dose for Tuberculous Meningitis
PULMONARY TUBERCULOSIS WITHOUT HIV INFECTION:
Option 1:
Initial regimen: 10 to 15 mg/kg IM or orally once a day (maximum 300 mg/day) PLUS rifampin, pyrazinamide, and ethambutol/streptomycin
- Duration of therapy: 8 weeks
Continuation regimen: 10 to 15 mg/kg IM or orally once a day (maximum 300 mg/day) OR 20 to 40 mg/kg IM or orally 2 to 3 times a week (maximum 900 mg/day) PLUS rifampin
- Duration of therapy: 16 weeks
Option 2:
Initial regimen: 10 to 15 mg/kg IM or orally once a day (maximum 300 mg/day) PLUS rifampin, pyrazinamide, and streptomycin/ethambutol
- Duration of therapy: 2 weeks
Followed by: 20 to 40 mg/kg IM or orally 2 times a week (maximum 900 mg/day) PLUS rifampin, pyrazinamide, and streptomycin/ethambutol
- Duration of therapy: 6 weeks
Continuation regimen: 20 to 40 mg/kg IM or orally 2 times a week (maximum 900 mg/day) PLUS rifampin
- Duration of therapy: 16 weeks
Option 3:
20 to 40 mg/kg IM or orally 3 times a week (maximum 900 mg/day) PLUS rifampin, pyrazinamide, and streptomycin/ethambutol
- Duration of therapy: 6 months
EXTRAPULMONARY TUBERCULOSIS:
Daily dosing: 10 to 15 mg/kg IM or orally once a day
- Maximum dose: 300 mg/day
Intermittent dosing: 20 to 40 mg/kg IM or orally 2 to 3 times a week
- Maximum dose: 900 mg/day
Duration of therapy:
- Extrapulmonary tuberculosis: 6 to 9 months
- Bone/joint tuberculosis: 12 months
- Miliary tuberculosis: 12 months
Comments:
- Doses given 2 or 3 times a week should be given via DOT.
- Adjunctive treatment (e.g., surgery, corticosteroids) may be necessary in patients with extrapulmonary tuberculosis.
- IM formulations may be used when oral administration is not possible.
Use: Treatment for all forms of susceptible tuberculosis
American Academy of Pediatrics (AAP) Recommendations:
Infants, Children, and Adolescents:
Daily dosing: 10 to 15 mg/kg orally once a day
- Maximum dose: 300 mg/day
Intermittent dosing: 20 to 30 mg orally 2 times a week
- Maximum dose: 900 mg/dose
Duration of therapy:
- Latent tuberculosis (drug-susceptible): 9 months
- Pulmonary and extrapulmonary tuberculosis (except meningitis): 2 months (3-drug regimen), then 4 months for drug-susceptible M tuberculosis OR 9 to 12 months for drug-susceptible Mycobacterium bovis
- Meningitis: 2 months (4-drug regimen), followed by 7 to 10 months of this drug and rifampin (once a day or 2 times a week)
Comments:
- Daily treatment is preferred for latent tuberculosis; however, DOT may be used if daily treatment is not possible.
- Patients who receive a 3-drug regimen (e.g., this drug, rifampin, and pyrazinamide) should have a low risk of drug resistance.
- Patients with only hilar adenopathy and a low risk of drug resistance may receive treatment with this drug and rifampin for 6 months.
- Patients with meningitis caused by M bovis should receive treatment with this drug, rifampin, and an aminoglycoside or ethionamide for 2 months, followed by at least 7 to 10 months of this drug and rifampin.
Uses:
- Treatment of latent Mycobacterial tuberculosis infection (e.g., positive tuberculin skin tests or interferon-gamma release assay result, no disease)
- Treatment of pulmonary and extrapulmonary Mycobacterial tuberculosis infection (except meningitis) caused by M tuberculosis or M bovis
- Treatment of meningitis caused by M tuberculosis or M bovis
ATS, US CDC, and IDSA Recommendations:
Less than 15 years OR up to 40 kg:
- Daily regimen: 10 to 15 mg/kg IM, IV, or orally once a day
- Intermittent regimen: 20 to 30 mg IM, IV, or orally 2 to 3 times a week
15 years and older AND/OR over 40 kg:
- Daily regimen: 5 mg/kg (usually 300 mg/day) IM, IV, or orally once a day
- Intermittent regimen: 15 mg/kg (up to 900 mg/dose) IM, IV, or orally 2 to 3 times a week
Comment: Pyridoxine 25 to 50 mg/day should be considered in all patients at risk of developing neuropathy; patients with peripheral neuropathy may be given 100 mg/day.
Use: Treatment of drug-susceptible tuberculosis
US HHS, NIH, HRSA, and US CDC Recommendations:
Children:
DRUG-SUSCEPTIBLE TUBERCULOSIS:
Intensive Phase: 10 to 15 mg/kg orally once a day PLUS rifampin, pyrazinamide, and ethambutol
Maximum dose: 300 mg/day
Duration of therapy: 2 months
Continuation Phase: 10 to 15 mg/kg (up to 300 mg/day) orally once a day PLUS rifampin OR 20 to 30 mg/kg IM or orally 3 times a week
Duration of therapy:
- Bone/joint disease or meningitis: Up to 10 months
- Intrathoracic disease, lymph node tuberculosis: 7 months
- Minimal disease and in the absence of significant immune compromise: 4 months
Comment: The total duration of treatment is at least 12 months for minimal disease, and 18 to 24 months after non-bacteriological diagnosis or after culture conversion.
Uses:
- First-line drug for the treatment of active tuberculosis caused by M tuberculosis
- Alternative drug (as part of a 3-drug regimen) for the treatment of fully drug-susceptible tuberculosis in the absence of significant immune compromise
Usual Pediatric Dose for Tuberculosis - Prophylaxis
Infants and children:
Daily dosing: 10 mg/kg IM or orally once a day
- Maximum dose: 300 mg/day
Intermittent dosing: 20 to 30 mg/kg IM or orally 2 times a week
- Maximum dose: 900 mg/dose
Duration of therapy:
- Close contact with newly diagnosed tuberculosis patients: At least 12 weeks
- Fibrotic pulmonary lesions or pulmonary silicosis: 12 months (or 4 months PLUS rifampin)
- Patients with HIV: At least 12 months
Comments:
- Bacteriologically positive or radiographically progressive tuberculosis should be excluded before starting treatment.
- Close contacts of persons with infectious tuberculosis within the past 3 months should be offered preventative therapy until a repeat skin test is performed 12 weeks after contact. If the skin test is positive, treatment should be continued.
- Pyridoxine is recommended in patients who are malnourished and those at risk of neuropathy (e.g., alcoholics, patients with diabetes).
- IM formulations may be used when oral administration is not possible.
Uses:
Preventive therapy in:
- High-incidence groups (e.g., foreign-born patients from high-prevalence countries who never received BCG vaccine, medically underserved, low-income populations, including high-risk racial or ethnic minority populations, especially blacks, Hispanics, and Native Americans, and residents of facilities for long-term care [e.g., correctional institutions, nursing homes, mental institutions])
- IV drug users known to be HIV-seronegative
- Patients less than 4 years with a greater than 10 mm induration from a purified protein derivative (PPD) Mantoux tuberculin test
- Patients who have a tuberculin skin test reaction of 15 mm or more
- Patients with HIV infection and persons with risk factors for HIV infection whose status is unknown, but who are suspected of having HIV infection
- Patients with the following medical conditions: clinical situations associated with substantial rapid weight loss/chronic undernutrition (e.g., carcinomas of the upper oropharynx and upper gastrointestinal tract that prevent adequate nutritional intake, chronic malabsorption syndromes, chronic peptic ulcer disease, intestinal bypass surgery, postgastrectomy state with/without weight loss), diabetes mellitus, end-stage renal disease, immunosuppressive therapy, prolonged adrenocorticosteroid therapy, silicosis, some hematologic and reticuloendothelial diseases (e.g., leukemia, Hodgkin's lymphoma)
- Persons with abnormal chest radiographs that show fibrotic lesions likely to represent old healed tuberculosis or pulmonary silicosis
- Recent converters (e.g., tuberculin skin test with at least a 10 mm increase within a 2 year period)
- Tuberculin-negative patients who have been close contacts of infectious persons within the past 3 months
US HHS, NIH, HRSA, and US CDC Recommendations:
Children:
First choice: 10 to 15 mg/kg orally once a day
Maximum dose: 300 mg/day
Duration of therapy: 9 months
Alternative choices:
Daily dosing: 10 to 15 mg/kg orally once a day PLUS rifampin
Maximum dose: 300 mg/day
Duration of therapy: 3 to 4 months
Intermittent dosing: 20 to 30 mg/kg orally 2 times a week
Maximum dose: 900 mg/day
Duration of therapy: 9 months
Comments:
- Intermittent dosing should be reserved for situations where adherence with daily treatment cannot be ensured.
- Patients receiving intermittent dosing should be given doses via DOT.
- Pyridoxine 1 to 2 mg/kg orally once a day (maximum dose 25 to 50 mg/day) should be given with this drug to exclusively breastfed infants, patients on meat- and milk-deficient diets, those with nutritional deficiencies, pregnant adolescents, and women.
- Tuberculosis must be excluded prior to starting post-treatment prophylaxis.
- Patients with documented severe adverse events may discontinue prophylaxis, but this is exceedingly rare.
Uses:
- Primary post-exposure prophylaxis of tuberculosis caused by M tuberculosis in patients with a positive tuberculin skin test (5 mm or greater) or interferon-gamma release assay without previous tuberculosis treatment
- Primary post-exposure prophylaxis of tuberculosis caused by Mycobacterium tuberculosis in patients with close contact with any infectious tuberculosis case (repeated exposures warrant repeated post-exposure prophylaxis)
Renal Dose Adjustments
Mild to moderate renal dysfunction: Data not available
Severe renal dysfunction: Frequent monitoring recommended.
ATS, US CDC, and IDSA Recommendations:
CrCl less than 30 mL/min: 300 mg IM, IV, or orally once a day OR 900 mg IM, IV, or orally 3 times a week
Liver Dose Adjustments
Use with caution.
Active chronic liver disease: Frequent monitoring recommended.
Acute liver disease of any etiology: Contraindicated
Patients with a previous drug-associated liver injury: Contraindicated
During treatment:
Transaminase values exceeding 3 to 5 times the upper limit of normal (3 to 5 x ULN): Temporarily discontinue this drug; restarting therapy should be given consideration.
Precautions
US BOXED WARNINGS:
- Severe and sometimes fatal hepatitis associated with therapy has been reported and may occur or may develop even after many months of treatment.
- The risk of developing hepatitis is age related. Approximate case rates by age are: less than 1 per 1000 persons under 20 years of age, 2 per 1000 persons in the 20 to 34-year age group, 12 per 1000 for persons in the 35 to 49-year age group, 23 per 1000 persons in the 50 to 64-year age group, and 8 per 1000 for persons over 65 years of age.
- The risk of hepatitis is increased with daily consumption of alcohol.
- Precise data to provide a fatality rate for drug-related hepatitis is not available; however, in a US Public Health Surveillance Study of 13,838 persons taking this drug, there were 8 deaths among 174 cases of hepatitis.
- Therefore, patients given this drug should be carefully monitored and interviewed at monthly intervals.
- For persons 35 and older, in addition to monthly symptom reviews, hepatic enzymes (specifically, AST and ALT [formerly SGOT and SGPT, respectively]) should be measured prior to starting therapy and periodically throughout treatment.
- Drug-associated hepatitis usually occurs during the first 3 months of treatment. Usually, enzyme levels return to normal despite continuance of drug, but in some cases, progressive liver dysfunction occurs.
- Other factors associated with an increased risk of hepatitis include daily use of alcohol, chronic liver disease and injection drug use.
- A recent report suggests an increased risk of fatal hepatitis associated with this drug among women, particularly black and Hispanic women. The risk may also be increased during the postpartum period.
- More careful monitoring should be considered in these groups, possibly including more frequent laboratory monitoring.
- If abnormalities of liver function exceed 3 to 5 x ULN, discontinuation of this drug should be strongly considered.
- Liver function tests are not a substitute for a clinical evaluation at monthly intervals or for the prompt assessment of signs/symptoms consistent with liver damage or other adverse effects. These include any of the following: unexplained anorexia, nausea, vomiting, dark urine, icterus, rash, persistent paresthesias of the hands and feet, persistent fatigue, weakness or fever of greater than 3 days duration and/or abdominal tenderness, especially right upper quadrant discomfort.
- If these symptoms appear or if signs suggestive of hepatic damage are detected, this drug should be discontinued promptly, since continued use of the drug in these cases has been reported to cause a more severe form of liver damage.
- Patients with tuberculosis who have hepatitis attributed to this drug should be given appropriate treatment with alternative drugs.
- If this drug must be reinstituted, it should be reinstituted only after symptoms and laboratory abnormalities have cleared.
- The drug should be restarted in very small and gradually increasing doses and should be withdrawn immediately if there is any indication of recurrent liver involvement.
- Preventative treatment should be deferred in persons with acute hepatic diseases.
CONTRAINDICATIONS:
- Hypersensitivity to the active ingredient or to any of the excipients, including drug-induced hepatitis
- Patients with acute liver disease of any etiology
- Previous hepatic injury associated with this drug
- Severe adverse reactions to this drug (e.g., drug fever, chills, arthritis)
Consult WARNINGS section for additional precautions.
Dialysis
Data not available
ATS, US CDC, and IDSA Recommendations:
Hemodialysis: 300 mg IM, IV, or orally once a day OR 900 mg IM, IV, or orally 3 times a week
Peritoneal dialysis: Data not available
Other Comments
Administration advice:
- Oral formulations should not be given with food.
- IM formulations: Exposure to low temperatures may result in crystallization. Vials should be warmed to room temperature before administration to allow the crystals to redissolve.
Storage requirements:
- Protect from light and moisture.
General:
- The Potts-Cozart test is a colorimetric urine test to assure patient compliance with this drug.
Monitoring:
- Hepatic: Periodic liver function tests
- Hypersensitivity: Signs/symptoms of hypersensitivity reactions
- Ocular: Periodic ophthalmic examinations in patients who develop visual symptoms
- Renal: Renal function tests
Patient advice:
- Inform patients that this drug may cause convulsions, optic neuritis, and/or psychosis, and they should avoid driving or operating machinery if these side effects occur.
- Advise patients to speak to their healthcare provider if they become pregnant, intend to become pregnant, or are breastfeeding.
