From the Guidelines
Latent tuberculosis infection (LTBI) should be treated with a 3-month course of once-weekly isoniazid plus rifapentine (3HP) as the preferred treatment option. This regimen consists of isoniazid 15 mg/kg (maximum 900 mg) and rifapentine 600-900 mg (based on weight) taken together once weekly for 12 weeks 1. Alternative regimens include 4 months of daily rifampin (10 mg/kg, maximum 600 mg daily), or 3 months of daily isoniazid plus rifampin.
Key Considerations
- All patients should receive pyridoxine (vitamin B6, 25-50 mg) with isoniazid to prevent peripheral neuropathy.
- Before starting treatment, active TB must be ruled out through symptom screening, chest X-ray, and sometimes sputum testing.
- Baseline liver function tests are recommended, especially for those with risk factors for hepatotoxicity.
- Monthly monitoring for adverse effects is essential, with particular attention to hepatotoxicity symptoms (nausea, vomiting, abdominal pain, jaundice).
High-Risk Groups
- Recent contacts of active TB cases
- HIV-positive individuals
- Those on immunosuppressive therapy
- Persons with fibrotic changes on chest X-ray
Benefits of Treatment
- Reduces the risk of progression to active TB by 60-90%
- Prevents both individual disease and community transmission The shorter rifampin-containing regimens are generally preferred due to better completion rates and fewer side effects 1.
From the FDA Drug Label
Although there have not been the same kinds of carefully conducted controlled trials of treatment of Extra pulmonary tuberculosis as for pulmonary disease, increasing clinical experience indicates that a 6 to 9 month short-course regimen is effective For Preventative Therapy of Tuberculosis Before isoniazid preventive therapy is initiated, bacteriologically positive or radiographically progressive tuberculosis must be excluded. Adults over 30 Kg: 300 mg per day in a single dose. Infants and Children: 10 mg/kg (up to 300 mg daily) in a single dose
The management of latent tuberculosis involves the use of isoniazid for preventative therapy. The recommended dosage is 300 mg per day for adults over 30 kg and 10 mg/kg (up to 300 mg daily) for infants and children. The treatment should be continued for a sufficient period, typically 6 to 9 months, to ensure effectiveness 2.
- Key considerations:
- Exclude bacteriologically positive or radiographically progressive tuberculosis before initiating preventative therapy
- Use isoniazid as the primary medication for preventative therapy
- Monitor patient compliance using methods such as the Potts-Cozart test or isoniazid test strips 2
- Consider concomitant administration of pyridoxine (B6) in malnourished patients or those predisposed to neuropathy 2
From the Research
Latent Tuberculosis Management Regimens
- The mainstay of treatment for latent tuberculosis infection is isoniazid (INH), with a recommended regimen of 9 months daily self-administered INH (9H) having an efficacy of more than 90% if completed properly 3.
- However, INH is associated with serious adverse events, including hepatotoxicity, which can be fatal, and requires close follow-up of patients, increasing the cost and complexity of treatment 3.
- Alternative regimens have been studied, including 2 months of rifampin and pyrazinamide, which has excellent efficacy in experimental studies and randomized trials, but is associated with an unacceptably high rate of severe liver toxicity in non-HIV-infected adults 3, 4.
- Other regimens, such as 3-4 months of INH and rifampin, and 4 months of rifampin, have shown equivalent effectiveness to 6 months INH, with better completion rates and less toxicity 3, 5.
Comparison of Regimens
- A systematic review and meta-analysis found that the 3-month regimen of isoniazid plus rifapentine (3HP) had less hepatotoxicity, better efficacy, and a better completion rate compared to the 9-month regimen of isoniazid (9H) 6.
- A population-based study found that treatment with 4 months of rifampin (4R) had lower frequencies of severe hepatic adverse events, higher treatment completion, and lower direct health system costs compared to 9H 5.
- A systematic review and meta-analysis found that the 3-month isoniazid-rifapentine regimen was as safe and effective as other recommended latent tuberculosis infection regimens, with significantly higher treatment completion rates 7.
Adverse Events and Completion Rates
- The risk of severe hepatotoxicity was higher with isoniazid than with rifampin, with an adjusted odds ratio of 2.3 (95% CI: 0.3-16.1) 5.
- The completion rate was higher for the 4-month rifampin regimen (53.5%) compared to the 9-month isoniazid regimen (36.9%), with an adjusted relative risk of 1.5 (95% CI: 1.3-1.7) 5.
- The 3-month isoniazid-rifapentine regimen had a higher treatment completion rate (87.5%) compared to other latent tuberculosis infection regimens (65.9%) 7.