What is the treatment regimen for latent Tuberculosis (TB)?

From the Guidelines

The most effective treatment regimen for latent Tuberculosis (TB) is 3 months of isoniazid plus rifapentine given once weekly, due to its excellent tolerability, efficacy, and higher completion rates compared to longer regimens. This regimen is preferred because it offers a shorter treatment duration, which enhances patient adherence and effectiveness in preventing the progression to active TB disease 1. The alternative regimens include rifampin daily for 4 months, isoniazid plus rifampin daily for 3 months, or isoniazid daily for 6-9 months.

Key Considerations for Treatment Regimens

• Isoniazid plus rifapentine once weekly for 3 months is the preferred regimen due to its strong evidence and moderate quality of evidence, especially for HIV-negative individuals 1.
• Rifampin daily for 4 months is another preferred option, with strong evidence and moderate quality of evidence, but its use in HIV-positive individuals lacks direct evidence 1.
• The choice of regimen should consider potential drug interactions, patient adherence concerns, and the possibility of drug-resistant TB.
• Pyridoxine (vitamin B6) should be administered with isoniazid to prevent peripheral neuropathy, typically at a dose of 25-50mg.

Monitoring and Adherence

Regular monitoring for side effects, particularly liver function tests for patients on isoniazid, is crucial. Completing the full treatment course is vital for effectively eliminating the latent infection and preventing progression to active TB disease. The guidelines from the National Tuberculosis Controllers Association and CDC in 2020 support the use of short-course rifamycin-based treatment regimens over longer-course isoniazid monotherapy for the treatment of LTBI, especially in the absence of drug intolerability or drug-drug interactions 1.

From the FDA Drug Label

PRIFTIN is indicated in adults and children 2 years and older for the treatment of latent tuberculosis infection caused by Mycobacterium tuberculosis in patients at high risk of progression to tuberculosis disease... PRIFTIN must always be used in combination with isoniazid as a 12-week once-weekly regimen for the treatment of latent tuberculosis infection

PRIFTIN should be administered once weekly in combination with isoniazid for 12 weeks as directly observed therapy.

The treatment regimen for latent Tuberculosis (TB) is a 12-week once-weekly regimen of rifapentine (PRIFTIN) in combination with isoniazid, administered as directly observed therapy 2.

• The recommended dose of PRIFTIN is determined based on the patient's weight, up to a maximum of 900 mg once weekly.
• The recommended dose of isoniazid is 15 mg/kg (rounded to the nearest 50 mg or 100 mg) up to a maximum of 900 mg once weekly for adults and children 12 years and older, and 25 mg/kg (rounded to the nearest 50 mg or 100 mg) up to a maximum of 900 mg once weekly for children 2 to 11 years.

From the Research

Treatment Regimens for Latent Tuberculosis (TB)

The treatment regimens for latent TB include:

• Once-weekly isoniazid plus rifapentine for 3 months 3
• Daily rifampin for 4 months 3
• Daily isoniazid plus rifampin for 3-4 months 3, 4
• Daily isoniazid for 6-9 months 3, 4, 5
• 2 months of rifampin and pyrazinamide, although this regimen is associated with an unacceptably high rate of severe liver toxicity in non-HIV-infected adults 4
• 4 months of rifampin, which has been found to have significantly better completion rates and less toxicity than 9 months of isoniazid 4

Efficacy and Safety of Treatment Regimens

The efficacy and safety of these regimens have been evaluated in several studies:

• A 9-month regimen of isoniazid alone has been shown to be effective in preventing TB disease, but is associated with hepatotoxicity and poor treatment completion rates 4, 5
• A 3-month regimen of isoniazid plus rifapentine has been shown to be as effective as 9 months of isoniazid alone, with higher treatment completion rates and less hepatotoxicity 6, 7
• A 4-month regimen of rifampin has been found to have similar efficacy to 9 months of isoniazid, with better treatment completion rates and less toxicity 4

Adverse Events

The adverse event profiles of these regimens have been evaluated in several studies:

• The INH/RPT-3 regimen (12 doses of isoniazid and rifapentine given once weekly) has been found to have a generally favorable adverse event profile, with flu-like reactions reported more frequently and hepatotoxicity reported less frequently than standard treatment 6
• The 4-month rifampin regimen has been found to have significantly less hepatotoxicity than the 9-month isoniazid regimen 4