From the Guidelines
Isoniazid (INH) is recommended for 6-9 months to prevent latent tuberculosis (TB) reactivation, with the 9-month regimen providing approximately 90% protection and the 6-month regimen offering about 70-80% protection, as supported by the most recent guidelines from the National Tuberculosis Controllers Association and CDC, 2020 1. The treatment duration is necessary because INH only works on actively metabolizing bacteria, and the dormant bacilli in latent TB periodically "wake up" at different times.
- The lengthy treatment ensures that most bacteria encounter the drug during their metabolically active phases.
- INH works by inhibiting the synthesis of mycolic acids, essential components of the mycobacterial cell wall, through blocking the enzyme InhA.
- Patients should take INH with vitamin B6 (pyridoxine) 25-50mg daily to prevent peripheral neuropathy, especially in those at higher risk (pregnant women, malnourished individuals, alcoholics, diabetics, HIV-positive patients, and those with kidney failure).
- Monthly monitoring for hepatotoxicity is recommended, particularly in those over 35 years old or with underlying liver disease, as noted in the guidelines from the National Tuberculosis Controllers Association and CDC, 2020 1. The standard regimen for latent TB treatment is INH 300mg daily for adults (10-15mg/kg/day for children, maximum 300mg) for 6-9 months, as recommended by the guidelines from the National Tuberculosis Controllers Association and CDC, 2020 1.
- Alternative regimens, such as 3-4 months of daily rifapentine plus isoniazid, or 3-4 months of isoniazid plus rifampicin, are also recommended, but the 6-9 month INH regimen remains a preferred option in certain cases, as noted in the guidelines from the National Tuberculosis Controllers Association and CDC, 2020 1.
- The evidence synthesis included multiple durations of isoniazid therapy in persons with a positive TST, demonstrating the benefit of LTBI treatment with isoniazid in this high-risk subset of patients with LTBI, as reported in the study published in the MMWR Recommendations and Reports, 2020 1.
From the Research
Isoniazid (INH) and Latent Tuberculosis (TB) Prevention
- Isoniazid (INH) is the mainstay of treatment for latent tuberculosis infection and has been used for almost 50 years 2.
- The currently recommended preferred regimen is 9 months of daily self-administered INH, which has an efficacy of more than 90% if completed properly 2.
- However, INH is associated with serious adverse events, including hepatotoxicity, which can be fatal in some cases 2.
Duration of INH Administration
- The standard duration of INH administration is 6-9 months, but this can be a limitation due to toxicity and low rates of treatment completion 3.
- Studies have shown that shorter regimens, such as 3 months of rifapentine and INH, can be as effective as 9 months of INH alone in preventing tuberculosis 3, 4.
- A 3-month regimen of INH and rifampin has also been shown to have equivalent effectiveness as 6 months of INH, but with similar completion rates and toxicity 2.
Alternative Regimens
- Other regimens, such as 2 months of pyrazinamide and rifampin, have been studied, but are associated with an unacceptably high rate of severe liver toxicity in non-HIV-infected adults 5, 2.
- A weekly regimen of rifapentine plus INH for 3 months has been shown to have higher completion rates and less liver toxicity than 9 months of INH, but with more treatment-limiting adverse events 3, 6.
- Rifampicin alone for 3-4 months has been found to have significantly better completion rates and less toxicity than 9 months of INH, but only one trial has evaluated its efficacy and effectiveness 2.