Why is Isoniazid (INH) used as prophylaxis for tuberculosis?

From the Guidelines

Isoniazid (INH) is used as prophylaxis for tuberculosis because it effectively prevents the development of active TB disease in individuals with latent TB infection, with a recommended regimen of 6-9 months of daily isoniazid, as supported by the most recent guidelines from the National Tuberculosis Controllers Association and CDC, 2020 1. The use of INH as prophylaxis for tuberculosis is based on its ability to inhibit the synthesis of mycolic acids, essential components of the mycobacterial cell wall, thereby killing dormant bacteria before they can cause active disease. This prophylaxis is particularly important for high-risk individuals, including recent contacts of TB patients, those with positive tuberculin skin tests or interferon-gamma release assays, HIV-positive individuals, and patients starting immunosuppressive therapy.

• Key points to consider when using INH as prophylaxis include:
  • The recommended duration of treatment is 6-9 months, with 6 months being strongly recommended for HIV-negative adults and children, and 9 months being conditionally recommended for adults and children, both HIV-negative and HIV-positive 1.
  • INH can cause hepatotoxicity, and patients should be monitored monthly for adherence, side effects, and symptoms of active TB.
  • Supplementation with vitamin B6 (pyridoxine) at 25-50 mg daily may be recommended to prevent peripheral neuropathy, especially in malnourished individuals, pregnant women, and those with conditions predisposing to neuropathy.
• The evidence supporting the use of INH as prophylaxis for tuberculosis is based on multiple studies, including a systematic review and meta-analysis of randomized controlled trials, which demonstrated that INH can reduce the risk of developing active TB by 60-90% 1.
• It is essential to note that the effectiveness of INH prophylaxis may vary depending on the population being treated, with some studies suggesting that INH may be more effective in children than in adults, and that the risk of hepatotoxicity may be lower in children than in adults 1.

From the FDA Drug Label

Isoniazid is recommended as preventive therapy for the following groups, regardless of age.

Candidates for preventive therapy who have HIV infection should have a minimum of 12 months of therapy.

Candidates for preventive therapy who have fibrotic pulmonary lesions consistent with healed tuberculosis or who have pulmonary silicosis should have 12 months of isoniazid or 4 months of isoniazid and rifampin, concomitantly.

Isoniazid (INH) is used as prophylaxis for tuberculosis in certain high-risk groups, including:

• Persons with HIV infection
• Close contacts of persons with newly diagnosed infectious tuberculosis
• Recent converters, as indicated by a tuberculin skin test
• Persons with abnormal chest radiographs that show fibrotic lesions likely to represent old healed tuberculosis
• Persons with certain medical conditions that increase the risk of tuberculosis, such as silicosis, diabetes mellitus, and immunosuppressive therapy
• Persons under the age of 35 with a tuberculin skin test reaction of 10 mm or more who are members of high-incidence groups 2. Key words: Isoniazid, prophylaxis, tuberculosis, high-risk groups.

From the Research

Rationale for Isoniazid (INH) Prophylaxis

• Isoniazid (INH) has been the mainstay of treatment for latent tuberculosis infection for almost 50 years, with a recommended regimen of 9 months of daily self-administered INH having an efficacy of more than 90% if completed properly 3.
• The use of INH as prophylaxis is due to its ability to effectively prevent the progression of latent tuberculosis infection to active tuberculosis, with studies showing that INH preventive therapy can reduce the incidence of tuberculosis disease in contacts of patients with multidrug-resistant tuberculosis 4.

Efficacy and Safety of INH Prophylaxis

• The efficacy of INH prophylaxis has been demonstrated in several studies, with a 3-month regimen of rifapentine plus isoniazid showing similar efficacy to 9 months of isoniazid alone in preventing tuberculosis 5.
• However, INH is associated with serious adverse events, including hepatotoxicity, which can limit its use as prophylaxis 3, 6, 7.
• Studies have shown that the adverse event profile of INH/RPT-3 (12 doses of isoniazid and rifapentine given once weekly) appears generally favorable, with lower hepatotoxicity compared to standard INH treatment 6, 7.

Alternative Regimens

• Several alternative regimens have been studied, including 2 months of rifampin and pyrazinamide, 3 to 4 months of INH and rifampin, and 4 months of rifampin, with varying degrees of efficacy and safety 3.
• The use of rifapentine plus isoniazid for 3 months has been shown to be as effective as 9 months of isoniazid alone in preventing tuberculosis, with a higher treatment-completion rate and lower hepatotoxicity 5.