Usual Adult Dose for Tuberculosis - Active

Initial phase: 600 mg orally twice a week for 2 months
Continuation phase: 600 mg orally once a week for 4 months

Comments:

• Limitations of Use:
• This drug should not be used as monotherapy in either the initial or the continuation phases of active antituberculous therapy.
• This drug should not be used once weekly in the continuation phase regimen in combination with isoniazid in HIV-infected patients with active pulmonary tuberculosis (TB) due to higher rate of failure and/or relapse with rifampin-resistant organisms.
• This drug has not been studied as part of the initial phase treatment regimen in HIV-infected patients with active pulmonary TB.
• This drug is only recommended for the treatment of active TB caused by drug-susceptible organisms as part of regimens consisting of a 2-month initial phase followed by a 4-month continuation phase.
• This drug should not be used in the treatment of active pulmonary TB caused by rifampin-resistant strains.
• Initial phase: This drug should be administered as directly observed therapy (DOT), with an interval of at least 3 consecutive days (72 hours) between doses, in combination with other antituberculosis (anti-TB) drugs as part of an appropriate regimen which includes daily companion drugs such as isoniazid, ethambutol, and pyrazinamide.
• Continuation phase: After the initial phase, this drug should be used in combination with isoniazid or another appropriate anti-TB drug for susceptible organisms administered as DOT.

Use: In combination with at least 1 anti-TB drug to which the isolate is susceptible, for the treatment of active pulmonary TB caused by Mycobacterium tuberculosis

American Thoracic Society (ATS), US CDC, and Infectious Diseases Society of America (IDSA) Recommendations: 10 to 20 mg/kg orally once a week

Comments:

• Recommended as a first-line drug for TB
• Patients who are not obese may be dosed based on actual weight; for obese patients (more than 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 x (actual weight - IBW)]), as is done for initial aminoglycoside doses.
• Because TB drug dosing has not been established for obese patients, therapeutic drug monitoring may be considered for such patients.
• Current guidelines should be consulted for additional information.

Usual Adult Dose for Tuberculosis - Latent

Weight 10 to 14 kg: 300 mg orally once a week
Weight 14.1 to 25 kg: 450 mg orally once a week
Weight 25.1 to 32 kg: 600 mg orally once a week
Weight 32.1 to 50 kg: 750 mg orally once a week
Weight greater than 50 kg: 900 mg orally once a week
Maximum dose: 900 mg/week
Duration of therapy: 12 weeks

Comments:

• Limitations of Use:
• Active TB disease should be ruled out prior to starting treatment for latent tuberculosis infection (LTBI).
• This drug must always be used in combination with isoniazid as a 12-week once-weekly regimen for the treatment of LTBI; this drug in combination with isoniazid is not recommended for patients presumed to be exposed to rifamycin-resistant or isoniazid-resistant M tuberculosis.
• This drug should be administered in combination with isoniazid as DOT.

Use: For the treatment of LTBI caused by M tuberculosis in patients at high risk of progression to TB disease (including those in close contact with active TB patients, recent conversion to a positive tuberculin skin test, patients with HIV, or those with pulmonary fibrosis on radiograph)

Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV Recommendations:
Preferred Regimen:

• Weight 32.1 to 49.9 kg: 750 mg orally once a week
• Weight at least 50 kg: 900 mg orally once a week

Maximum dose: 900 mg/week
Duration of therapy: 12 weeks

Alternative Regimen:

• Weight less than 35 kg: 300 mg orally once a day
• Weight 35 to 45 kg: 450 mg orally once a day
• Weight greater than 45 kg: 600 mg orally once a day

Maximum dose: 600 mg/day
Duration of therapy: 4 weeks

Comments:

• With isoniazid plus pyridoxine, recommended as a preferred and an alternate regimen for treating LTBI to prevent TB in patients with HIV; recommended in patients with positive screening test for LTBI, no evidence of active TB disease, and no history of treatment for active disease/latent TB infection OR in patients with close contact with a person with infectious TB (regardless of screening test result)
• Preferred regimen: This drug is recommended only for virally-suppressed patients receiving a raltegravir-, efavirenz-, or once-daily dolutegravir-based antiretroviral (ARV) regimen.
• Alternative regimen: This drug is recommended only for patients receiving an efavirenz-based ARV regimen.
• Current guidelines should be consulted for additional information.

Usual Pediatric Dose for Tuberculosis - Active

12 years and older:

• Initial phase: 600 mg orally twice a week for 2 months
• Continuation phase: 600 mg orally once a week for 4 months

Comments:

• Limitations of Use:
• This drug should not be used as monotherapy in either the initial or the continuation phases of active antituberculous therapy.
• This drug should not be used once weekly in the continuation phase regimen in combination with isoniazid in HIV-infected patients with active pulmonary TB due to higher rate of failure and/or relapse with rifampin-resistant organisms.
• This drug has not been studied as part of the initial phase treatment regimen in HIV-infected patients with active pulmonary TB.
• This drug is only recommended for the treatment of active TB caused by drug-susceptible organisms as part of regimens consisting of a 2-month initial phase followed by a 4-month continuation phase.
• This drug should not be used in the treatment of active pulmonary TB caused by rifampin-resistant strains.
• Initial phase: This drug should be administered as DOT, with an interval of at least 3 consecutive days (72 hours) between doses, in combination with other anti-TB drugs as part of an appropriate regimen which includes daily companion drugs such as isoniazid, ethambutol, and pyrazinamide.
• Continuation phase: After the initial phase, this drug should be used in combination with isoniazid or another appropriate anti-TB drug for susceptible organisms administered as DOT.

Use: In combination with at least 1 anti-TB drug to which the isolate is susceptible, for the treatment for active pulmonary TB caused by M tuberculosis

ATS, US CDC, and IDSA Recommendations:
12 years and older: 10 to 20 mg/kg orally once a week

Comments:

• Recommended as a first-line drug for TB
• Patients who are not obese may be dosed based on actual weight; for obese patients (more than 20% above IBW), dosing based on IBW may be preferred for initial doses.
• Some clinicians prefer a modified IBW (IBW + [0.40 x (actual weight - IBW)]), as is done for initial aminoglycoside doses.
• Because TB drug dosing has not been established for obese patients, therapeutic drug monitoring may be considered for such patients.
• Current guidelines should be consulted for additional information.

Usual Pediatric Dose for Tuberculosis - Latent

2 years and older:

• Weight 10 to 14 kg: 300 mg orally once a week
• Weight 14.1 to 25 kg: 450 mg orally once a week
• Weight 25.1 to 32 kg: 600 mg orally once a week
• Weight 32.1 to 50 kg: 750 mg orally once a week
• Weight greater than 50 kg: 900 mg orally once a week

Maximum dose: 900 mg/week
Duration of therapy: 12 weeks

Comments:

• Limitations of Use:
• Active TB disease should be ruled out prior to starting treatment for LTBI.
• This drug must always be used in combination with isoniazid as a 12-week once-weekly regimen for the treatment of LTBI; this drug in combination with isoniazid is not recommended for patients presumed to be exposed to rifamycin-resistant or isoniazid-resistant M tuberculosis.
• This drug should be administered in combination with isoniazid as DOT.

Use: For the treatment of LTBI caused by M tuberculosis in patients at high risk of progression to TB disease (including those in close contact with active TB patients, recent conversion to a positive tuberculin skin test, patients with HIV, or those with pulmonary fibrosis on radiograph)

Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV Recommendations:
Preferred Regimen:

• Weight 32.1 to 49.9 kg: 750 mg orally once a week
• Weight at least 50 kg: 900 mg orally once a week

Maximum dose: 900 mg/week
Duration of therapy: 12 weeks

Alternative Regimen:

• Weight less than 35 kg: 300 mg orally once a day
• Weight 35 to 45 kg: 450 mg orally once a day
• Weight greater than 45 kg: 600 mg orally once a day

Maximum dose: 600 mg/day
Duration of therapy: 4 weeks

Comments:

• With isoniazid plus pyridoxine, recommended as a preferred and an alternate regimen for treating LTBI to prevent TB in patients with HIV; recommended in patients with positive screening test for LTBI, no evidence of active TB disease, and no history of treatment for active disease/latent TB infection OR in patients with close contact with a person with infectious TB (regardless of screening test result)
• Preferred regimen: This drug is recommended only for virally-suppressed patients receiving a raltegravir-, efavirenz-, or once-daily dolutegravir-based ARV regimen.
• Alternative regimen: This drug is recommended only for patients receiving an efavirenz-based ARV regimen.
• Current guidelines should be consulted for additional information.

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Patients with abnormal liver tests and/or liver disease or those starting treatment for active pulmonary TB: This drug should only be used in cases of necessity and under strict medical supervision; frequent monitoring recommended.

If evidence of liver injury occurs during therapy: This drug should be discontinued.

Precautions

CONTRAINDICATIONS:

• History of hypersensitivity to rifamycins

Safety and efficacy in the treatment of active pulmonary TB have not been established in patients younger than 12 years.
Safety and efficacy in the treatment of LTBI have not been established in patients younger than 2 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• Administer with meals; administration with a meal increases bioavailability and may reduce the incidence of gastrointestinal upset, nausea, and/or vomiting.
• For patients who cannot swallow tablets, the tablets may be crushed and added to a small amount of semi-solid foods, all of which should be consumed immediately.

Storage requirements:

• Store at 25C (77F); excursions permitted to 15C to 30C (59F to 86F).
• Protect from excessive heat and humidity.

Monitoring:

• Hepatic: For symptoms of liver injury; serum transaminase levels in patients with abnormal liver tests and/or liver disease or those starting treatment for active pulmonary TB (before therapy and every 2 to 4 weeks during therapy)
• Hypersensitivity: For signs/symptoms of hypersensitivity reactions
• Infections/Infestations: For signs/symptoms of TB relapse in patients with cavitary pulmonary lesions and/or positive sputum cultures after initial phase of active TB therapy and in those with evidence of bilateral pulmonary disease

Patient advice:

• Read the US FDA-approved patient labeling (Medication Guide).
• Avoid missing doses and complete the entire course of therapy.
• Stop this drug and contact health care provider if signs/symptoms of hypersensitivity reactions (e.g., influenza-like illness, hypotension, urticaria, angioedema, bronchospasm, conjunctivitis, thrombocytopenia, neutropenia) occur.
• Stop this drug immediately and promptly report the first signs/symptoms of skin rash, mucosal lesions, or any other sign of hypersensitivity.
• Stop this drug and notify physician promptly if any signs/symptoms of hepatitis (e.g., fever, loss of appetite, malaise, nausea/vomiting, darkened urine, yellowish discoloration of the skin and eyes, pain/swelling of the joints) occur.
• This drug produces a red-orange discoloration of sputum, sweat, tears, breast milk, and urine; contact lenses or dentures may be permanently stained.
• Contact physician at once if diarrhea occurs while taking or after stopping this drug.
• Monitor infants exposed to this drug through breast milk for signs of hepatotoxicity to include irritability, prolonged unexplained crying, yellowing of the eyes, loss of appetite, vomiting, and darkening urine/lightening stool (pale or light brown).
• Use of this drug may reduce the efficacy of hormonal contraceptives. If you use hormonal contraceptives, use an alternative nonhormonal contraceptive method or add a barrier method of contraception during therapy.