Usual Adult Dose for Mycobacterium avium-intracellulare - Prophylaxis

300 mg orally once a day

Comment: Patients with a tendency to develop gastrointestinal side effects (e.g., nausea, vomiting) may be given 150 mg orally 2 times a day with food.

Use: Prevention of disseminated Mycobacterium avium-intracellulare complex (MAC) disease in patients with advanced HIV

Infectious Diseases Society of America (IDSA) and American Thoracic Society (ATS) Recommendations:
300 mg orally once a day

Use: Alternative option for the prevention of disseminated MAC disease in patients with HIV

US Department of Health and Human Services (US HHS), National Institutes of Health (NIH), Health Resources and Services Administration (HRSA), and US Centers for Disease Control and Prevention (US CDC) Recommendations:
300 mg orally once a day

Comments:

• The dose should be adjusted based on concomitant antiretroviral therapy.
• Active tuberculosis should be ruled out prior to starting treatment.
• Primary prophylaxis may be discontinued in patients with a CD4 count of greater than 100 cells/mm3 for greater than 3 consecutive months in response to antiretroviral therapy (ART).
• Primary prophylaxis should be restarted in patients with a CD4 count of less than 50 cells/mm3.

Use: Alternative primary prophylaxis of disseminated MAC disease in patients with HIV and CD4 counts less than 50 cells/mm3 (after during out disseminated MAC disease based on clinical assessment)

Usual Adult Dose for Mycobacterium avium-intracellulare - Treatment

IDSA and ATS Recommendations:
Severe Nodular/Bronchiectatic or Fibrocavitary Disease OR Previously Treated Disease:

• Preferred regimen: 300 mg orally once a day PLUS ethambutol and clarithromycin
• Alternative regimen: 300 to 400 mg orally once a day PLUS ethambutol and azithromycin

Comments:

• Patients may require additional treatment with streptomycin or amikacin for the first 2 to 3 months.
• Patients weighing less than 50 kg should be given a daily dose of 150 mg/day.
• Some experts recommend beginning treatment with the macrolide first, then starting this drug at an attenuated dose, with gradual dose increases to the desired therapeutic level over 1 to 2 weeks.

Uses:

• Preferred treatment (with clarithromycin and ethambutol) of disseminated MAC disease in patients with HIV
• Alternative treatment (with azithromycin and ethambutol) of disseminated MAC disease in patients with HIV

US HHS, NIH, HRSA, and US CDC Recommendations:
300 mg orally once a day

Comments:

• The dose should be adjusted based on concomitant antiretroviral therapy.
• Secondary prophylaxis/chronic maintenance may be discontinued in patients who have completed at least 12 months of MAC therapy, are asymptomatic for signs/symptoms of MAC, and have a sustained (greater than 6 months) CD4 count of greater than 100 cells/mm3 in response to ART.
• Secondary prophylaxis/chronic maintenance should be restarted in patients with a CD4 count of less than 100 cells/mm3.
• This drug may be considered as a third or fourth drug in patients with advanced immunosuppression (e.g., CD4 counts less than 50 cells/mcL), high mycobacterial loads (greater than 2 log CFU/mL), or in the absence of effective antiretroviral therapy.

Use: Third or fourth drug option as an alternative treatment in patients with disseminated MAC disease

Usual Adult Dose for Tuberculosis - Prophylaxis

US HHS, NIH, HRSA, and US CDC Recommendations:
Intensive phase: 5 mg/kg orally once a day PLUS isoniazid, ethambutol, and pyrazinamide
Maximum dose: 300 mg/day
Duration of therapy: 4 months

Comment: The dose should be adjusted based on concomitant antiretroviral therapy.

Uses:

• Alternative 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
• Alternative treatment to prevent tuberculosis in patients with close contact with a person with infectious tuberculosis, regardless of a screening test result

Usual Adult Dose for Tuberculosis - HIV Positive

IDSA, US CDC, and ATS Recommendations:
DRUG-SUSCEPTIBLE TUBERCULOSIS:
10 mg/kg orally once a day OR once a week

• Maximum dose: 300 mg/day

Comment: Doses given 2 times or 3 times a week are not recommended.

Use: Treatment of drug-susceptible tuberculosis

US HHS, NIH, HRSA, and US CDC Recommendations:
DRUG-SUSCEPTIBLE TUBERCULOSIS:
Intensive phase: 5 mg/kg orally once a day PLUS isoniazid, ethambutol, and pyrazinamide
Maximum dose: 300 mg/day
Duration of therapy: 2 months

Continuation phase: 5 mg/kg orally once a day for 5 to 7 days per week PLUS isoniazid
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:
Empiric therapy for suspected resistance to rifamycin and/or resistance to other drugs: 5 mg/kg orally once a day PLUS moxifloxacin/levofloxacin, ethambutol, isoniazid, pyrazinamide, and an aminoglycoside/capreomycin

Resistant to Isoniazid:
Intensive phase: 5 mg/kg orally once a day PLUS ethambutol, pyrazinamide, and moxifloxacin/levofloxacin
Maximum dose: 300 mg/day
Duration of therapy: 2 months

Continuation phase: 5 mg/kg orally once a day PLUS ethambutol and moxifloxacin/levofloxacin
Maximum dose: 300 mg/day
Duration of therapy: 7 months

Comments:

• If the organism is susceptible to this drug and isoniazid, ethambutol may be discontinued during the intensive phase.
• DOT is recommended for patients with HIV-related tuberculosis.
• Empiric therapy should be modified upon receiving drug susceptibility results.

Uses:

• First-line drug for the treatment of active tuberculosis caused by Mycobacterium tuberculosis
• Empiric treatment of patients with HIV with clinical and radiographic presentation suggestive of HIV-related tuberculosis

Usual Pediatric Dose for Mycobacterium avium-intracellulare - Treatment

US HHS, NIH, HRSA, and US CDC Recommendations:
Children:
TREATMENT:
Severe disease: 10 to 20 mg/kg orally once a day
Maximum dose: 300 mg/day
Duration of therapy: At least 12 months

Children older than 5 years:
PROPHYLAXIS:
Primary prophylaxis: 300 mg orally once a day with food
Secondary prophylaxis (chronic suppressive therapy): 5 mg/kg orally once a day with food

• Maximum dose: 300 mg/day

Comments:

• After at least 6 months of combined antiretroviral therapy (cART), primary prophylaxis may be discontinued in patients 2 to less than 6 years with a CD4 count of greater than 200 cells/mm3 for greater than 3 consecutive months OR patients 6 years and older with a CD4 count of greater than 100 cells/mm3 for greater than 3 consecutive months.
• Primary prophylaxis should be restarted in patients less than 6 years with a CD4 count less than 200 cells/mm3 OR patients 6 years and older with a CD4 count of less than 100 cells/mm3.
• After at least 6 months of cART, at least 12 months of MAC therapy, and asymptomatic for signs/symptoms of MAC, secondary prophylaxis may be discontinued in patients 5 to less than 6 years with a CD4 count of greater than 200 cells/mm3 for greater than 6 consecutive months OR patients 6 years and older with a CD4 count of greater than 100 cells/mm3 for greater than 6 consecutive months.
• Primary prophylaxis should be restarted in patients 5 to less than 6 years with a CD4 count less than 200 cells/mm3 OR patients 6 years and older with a CD4 count of less than 100 cells/mm3.

Uses:

• Alternative primary prophylaxis of MAC infections in patients 5 to 6 years with CD4 counts less than 75 cells/mm3
• Alternative primary prophylaxis of MAC infections in patients 6 years and older with CD4 counts less than 50 cells/mm3
• Alternative secondary prophylaxis (chronic suppressive therapy) of MAC infections in patients over 5 years with prior disease who received this drug as part of initial treatment

Usual Pediatric Dose for Mycobacterium avium-intracellulare - Prophylaxis

US HHS, NIH, HRSA, and US CDC Recommendations:
Children:
TREATMENT:
Severe disease: 10 to 20 mg/kg orally once a day
Maximum dose: 300 mg/day
Duration of therapy: At least 12 months

Children older than 5 years:
PROPHYLAXIS:
Primary prophylaxis: 300 mg orally once a day with food
Secondary prophylaxis (chronic suppressive therapy): 5 mg/kg orally once a day with food

• Maximum dose: 300 mg/day

Comments:

• After at least 6 months of combined antiretroviral therapy (cART), primary prophylaxis may be discontinued in patients 2 to less than 6 years with a CD4 count of greater than 200 cells/mm3 for greater than 3 consecutive months OR patients 6 years and older with a CD4 count of greater than 100 cells/mm3 for greater than 3 consecutive months.
• Primary prophylaxis should be restarted in patients less than 6 years with a CD4 count less than 200 cells/mm3 OR patients 6 years and older with a CD4 count of less than 100 cells/mm3.
• After at least 6 months of cART, at least 12 months of MAC therapy, and asymptomatic for signs/symptoms of MAC, secondary prophylaxis may be discontinued in patients 5 to less than 6 years with a CD4 count of greater than 200 cells/mm3 for greater than 6 consecutive months OR patients 6 years and older with a CD4 count of greater than 100 cells/mm3 for greater than 6 consecutive months.
• Primary prophylaxis should be restarted in patients 5 to less than 6 years with a CD4 count less than 200 cells/mm3 OR patients 6 years and older with a CD4 count of less than 100 cells/mm3.

Uses:

• Alternative primary prophylaxis of MAC infections in patients 5 to 6 years with CD4 counts less than 75 cells/mm3
• Alternative primary prophylaxis of MAC infections in patients 6 years and older with CD4 counts less than 50 cells/mm3
• Alternative secondary prophylaxis (chronic suppressive therapy) of MAC infections in patients over 5 years with prior disease who received this drug as part of initial treatment

Usual Pediatric Dose for Tuberculosis - Active

US HHS, NIH, HRSA, and US CDC Recommendations:
DRUG-SUSCEPTIBLE TUBERCULOSIS:
Children:
Initial phase: 10 to 20 mg/kg orally once a day OR 3 times a week PLUS ethambutol, isoniazid, and pyrazinamide
Maximum dose: 300 mg/day
Duration of therapy: 2 months

Continuation phase: 10 to 20 mg/kg orally once a day OR 3 times a week PLUS isoniazid
Maximum dose: 300 mg/day
Duration of therapy: 7 months

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

IDSA, US CDC, and ATS Recommendations:
Children: 5 mg/kg orally once a day OR once a week

• Maximum dose: 300 mg/day

Comment: The appropriate dose for children is unknown.

Use: Treatment of drug-susceptible tuberculosis

Renal Dose Adjustments

Mild to moderate renal dysfunction (CrCl 30 mL/min and greater): No adjustment recommended.
Severe renal dysfunction (CrCl less than 30 mL/min): Consider decreasing the dose by 50% if toxicity is suspected.

US HHS, NIH, HRSA, and US CDC Recommendations:
CrCl less than 30 mL/min: Reduce the daily dose by 50%, and consider therapeutic drug monitoring.

Liver Dose Adjustments

Mild liver dysfunction: No adjustment recommended.
Moderate to severe liver dysfunction: Data not available

Dose Adjustments

Concomitant use with:

• Amprenavir: Reduce the dose of this drug by at least 50% and monitor for adverse reactions.
• Clarithromycin: Patients should be monitored for adverse events; the dose should be reduced or the drug should be suspended if toxicity is suspected.
• Delavirdine: Contraindicated
• Fluconazole: Patients should be monitored for adverse events; the dose should be reduced or the drug should be suspended if toxicity is suspected.
• Indinavir: Reduce the dose of this drug by 50% and increase the dose of indinavir to 800 to 1000 mg orally 3 times a day for 10 days.
• Nelfinavir: Reduce the dose of this drug by 50% and increase the dose of nelfinavir to 1250 mg orally 2 times a day.
• Ritonavir or ritonavir-boosted fosamprenavir, lopinavir, saquinavir, OR tipranavir: Reduce the dose of this drug by at least 75% (to 150 mg/day maximum every other day or 3 times per week) and monitor for adverse reactions. If needed, the dose of this drug may be reduced further.
• Voriconazole: Contraindicated

IDSA, US CDC, and ATS Recommendations:
Nodular/Bronchiectatic Disease:
Older Patients:

• With concomitant clarithromycin use: 150 mg orally once a day

Signs/symptoms of toxicity: The dose should be decreased.

US HHS, NIH, HRSA, and US CDC Recommendations:
Active Tuberculosis:
Adults:

• With protease inhibitors (PIs): 150 mg orally once a day
• With efavirenz (EFV): 450 to 600 mg orally once a day
• With tenofovir alafenamide (TAF) OR elvitegravir (EVG)/cobicistat (COBI)-containing regimens: Not recommended.

Precautions

CONTRAINDICATIONS:

• Hypersensitivity to the active component, other rifamycins (e.g., rifampin/rifampicin), or any of the ingredients

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• This drug may be given at any time of the day without regard to meals.

Storage requirements:

• Store below 25C.

General:

• Food may decrease gastrointestinal upset, nausea, and/or vomiting.

Monitoring:

• Hematologic: Periodic platelet and white blood cell counts
• Hepatic: Periodic liver function tests
• Ocular: Signs/symptoms of uveitis (when used with macrolides or triazole antifungal agents)

Patient advice:

• Patients should be advised to avoid missing doses and to complete the entire course of therapy.
• Patients should be warned that treatment may produce a discoloration of sputum, sweat, tears, teeth, and urine; soft contact lenses may be permanently stained.
• Patients should be instructed to report signs/symptoms of Clostridium difficile (e.g., watery/bloody stools, stomach cramps, fever), for up to 2 months after stopping treatment.
• Patients should be told to immediately report cough, darkened urine, fever, joint pain/swelling, loss of appetite, malaise, nausea and vomiting, rash with fever/blisters with/without peeling skin, shortness of breath, swollen lymph nodes, yellowish discoloration of the skin and eyes, or wheezing.
• Advise patients to speak to their healthcare provider if they become pregnant, intend to become pregnant, or are breastfeeding.