Rifapentine in Tuberculosis Preventive Therapy
The recommended regimen for tuberculosis preventive therapy (TPT) using rifapentine is 12 once-weekly doses of rifapentine 900 mg plus isoniazid 900 mg (3HP regimen), administered over 3 months, which is a preferred first-line option for latent TB infection in adults and children aged 2 years and older. 1, 2, 3
Dosing by Age and Weight
Adults and Children ≥12 Years
- Rifapentine dose is weight-based up to 900 mg maximum once weekly 3
- Isoniazid 15 mg/kg (rounded to nearest 50-100 mg) up to 900 mg maximum once weekly 3
Children 2-11 Years
- Rifapentine dose is weight-based up to 900 mg maximum once weekly 3
- Isoniazid 25 mg/kg (rounded to nearest 50-100 mg) up to 900 mg maximum once weekly 3
Weight-based rifapentine dosing: 3
- 10-14 kg: 300 mg (2 tablets)
- 14.1-25 kg: 450 mg (3 tablets)
- 25.1-32 kg: 600 mg (4 tablets)
- 32.1-50 kg: 750 mg (5 tablets)
50 kg: 900 mg (6 tablets)
Administration and Monitoring
The 3HP regimen should be administered as directly observed therapy (DOT) or self-administered therapy (SAT) in persons aged ≥2 years, with all 12 doses taken with food to increase bioavailability and reduce gastrointestinal side effects. 1, 3
Monthly clinical evaluations (in-person or telephone) are required throughout the 12-week course to assess adherence and monitor for adverse effects. 2, 4
Baseline liver function tests are indicated only for patients with risk factors including abnormal liver tests, pre-existing liver disease, HIV infection, pregnancy, heavy alcohol use, or history of liver injury. 4
Treatment Completion Criteria
Treatment completion requires all 12 doses to be administered, as the regimen was designed and tested as a complete 12-dose course—stopping at 10 doses means the patient has not received full therapeutic benefit. 2
The 3HP regimen achieves substantially higher treatment completion rates (82.1%) compared to 9 months of isoniazid monotherapy (69.0%). 1, 5
Safety Profile and Adverse Events
Approximately 4% of patients experience flu-like reactions that typically occur 4 hours after medication ingestion, but permanent discontinuation due to adverse events occurs in only a small percentage of patients. 2
The 3HP regimen has significantly lower hepatotoxicity rates (0.4%) compared to 9 months of isoniazid (2.7%), though it has higher rates of treatment-related adverse events leading to discontinuation (4.9% vs 3.7%). 5, 6
Only discontinue 3HP permanently if symptoms suggestive of a systemic drug reaction occur—transient flu-like symptoms alone do not require discontinuation. 2
Special Population Considerations
HIV-Infected Patients
The 3HP regimen is recommended for HIV-infected persons taking antiretroviral medications with acceptable drug-drug interactions with rifapentine. 1
Rifapentine can be safely administered with dolutegravir-based antiretroviral therapy without dose adjustments, though it decreases dolutegravir area under the curve by 26%. 7
Rifapentine is contraindicated with protease inhibitors and certain NNRTIs (ritonavir, hard-gel saquinavir, delavirdine). 1, 4
Pregnant Women
For HIV-infected pregnant women, initiation of preventive therapy should not be delayed based on pregnancy alone, though the 9-month isoniazid regimen is the only recommended option during pregnancy—not 3HP. 4
Critical Contraindications
Active TB disease must be ruled out before initiating treatment for latent TB infection. 4, 3
Rifapentine is contraindicated in patients with hypersensitivity to rifamycins. 3
The 3HP regimen is not recommended for individuals presumed to be exposed to rifamycin-resistant or isoniazid-resistant M. tuberculosis. 3
Comparison to Alternative Regimens
The CDC recommends 3HP or 4 months of daily rifampin as preferred regimens over traditional 6-9 months of isoniazid monotherapy due to superior completion rates and safety profiles. 4
Network meta-analysis shows 3HP provides higher treatment completion than 4 months of rifampin (adjusted risk ratio 1.06), but with higher risk of adverse events leading to discontinuation (adjusted risk ratio 2.86). 6
No difference in efficacy for preventing tuberculosis disease has been found between 3HP and 4 months of rifampin. 6
Common Pitfalls to Avoid
Never use rifapentine as monotherapy—it must always be combined with isoniazid for latent TB infection treatment. 3
Do not use 3HP once weekly in HIV-infected patients with active pulmonary tuberculosis due to higher rates of failure and relapse with rifampin-resistant organisms. 3
For active TB treatment (not latent infection), rifapentine dosing is completely different: 600 mg twice weekly for 2 months, then 600 mg once weekly for 4 months, always with companion drugs. 1, 3