Rifapentine
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Rifapentine: From Pulmonary Tuberculosis to Leprosy
One-Sentence Summary
Rifapentine is a rifamycin antibiotic, originally used to treat pulmonary tuberculosis. The TxGNN model predicts it may be effective for leprosy (the top-ranked prediction), but no clinical trials are registered for this indication, and the evidence consists of 20 publications, only a few of which are clinical. A separate, much better-supported extension is TB prevention and treatment in people with HIV (rank 4), which has Phase 3 trial evidence.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Pulmonary tuberculosis |
| Predicted New Indication | Leprosy |
| TxGNN Prediction Score | 99.77% |
| Evidence Level | L3 (leprosy); the HIV-related extension is graded L1, but that grade applies to TB in people with HIV, not to HIV infection itself |
| US Market Status | Cancelled only (the only NDA on record is listed as cancelled) |
| Number of NDAs | 1 |
| Recommended Decision | Hold (leprosy: research question; the HIV-associated TB extension may Proceed with Guardrails) |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data is not available in the data compiled for this report. Based on what is known, rifapentine is a rifamycin that inhibits bacterial DNA-dependent RNA polymerase (rpoB). Its efficacy in tuberculosis is established.
Mycobacterium leprae is susceptible to rifamycins, and rifampicin is already a cornerstone of leprosy treatment and post-exposure prophylaxis. Mouse footpad studies suggest rifapentine has stronger bactericidal activity against M. leprae than rifampicin. A 2023 study in the New England Journal of Medicine evaluated single-dose rifapentine in household contacts of leprosy patients. The link is therefore biologically plausible, since it is an extension within the same drug class against a closely related mycobacterium.
The design, phase and results of the household-contact publications cannot be confirmed from titles alone and need full-text verification before the evidence level can be raised.
Clinical Trial Evidence
Currently no related clinical trials are registered for leprosy.
For reference, the second-best-supported prediction, HIV-associated tuberculosis (rank 4), has the following most relevant trials. These concern TB in people with HIV, not HIV treatment itself.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT01404312 | Phase 3 | Completed | 3000 | 4-week rifapentine + isoniazid vs 9-month isoniazid for TB prevention in HIV-infected people |
| NCT00057122 | Phase 3 | Completed | 1148 | Three TB prevention regimens vs 6 months of isoniazid in HIV-positive adults in Soweto |
| NCT05118490 | Phase 4 | Active, not recruiting | 1000 | Treatment completion of daily 1-month (1HP) vs weekly 3-month (3HP) rifapentine + isoniazid |
| NCT05122026 | Phase 1/2 | Active, not recruiting | 252 | Safety and dolutegravir pharmacokinetics with 1HP/3HP in pregnant people with HIV |
| NCT04272242 | Phase 2 | Terminated | 37 | Rifapentine–dolutegravir interaction in HIV/LTBI co-infection |
| NCT03510468 | Phase 1 | Completed | 51 | Effect of weekly rifapentine + isoniazid on tenofovir alafenamide pharmacokinetics |
| NCT03886701 | Phase 1 | Completed | 11 | Effect of weekly rifapentine + isoniazid on doravirine pharmacokinetics |
| NCT00002192 | Phase 2 | Completed | Not reported | Rifapentine tolerance and activity in AIDS patients with M. avium complex bacteremia |
Literature Evidence
Leprosy (rank 1)
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 37195940 | 2023 | Prophylaxis study (design to be verified) | N Engl J Med | Single-dose rifapentine in household contacts of leprosy patients |
| 37585641 | 2023 | Commentary/companion (to be verified) | N Engl J Med | Related report on rifapentine in household contacts |
| 40278757 | 2025 | Review | Trop Med Infect Dis | Efficacy, safety and feasibility of rifamycin-based post-exposure chemoprophylaxis for leprosy |
| 38440733 | 2024 | Review | Front Immunol | Leprosy treatment, prevention and immune response; notes rifampicin resistance as a concern |
| 32936818 | 2020 | Preclinical | PLoS Negl Trop Dis | Post-exposure prophylaxis efficacy of rifampin, rifapentine and other drugs in a mouse footpad model |
| 30207440 | 2016 | Preclinical | Indian J Lepr | Antibacterial activity of rifapentine and combinations in a murine model of rifampicin-resistant leprosy |
| 29071280 | 2017 | Molecular simulation | Mol Biol Res Commun | Assessment of rifabutin and rifapentine as replacements for rifampicin in drug-resistant leprosy |
| 11201894 | 2000 | Preclinical | Lepr Rev | Rifapentine–moxifloxacin–minocycline combination for leprosy, suited to monthly dosing |
HIV-associated tuberculosis (rank 4), key RCTs
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 30865794 | 2019 | RCT | N Engl J Med | One month of rifapentine + isoniazid to prevent HIV-related TB |
| 33951360 | 2021 | RCT (Phase 3) | N Engl J Med | Four-month rifapentine regimens with or without moxifloxacin for TB |
| 36041016 | 2023 | Clinical trial subgroup | Clin Infect Dis | Rifapentine ± moxifloxacin for pulmonary TB in people with HIV (S31/A5349) |
US Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| NDA021024 (cancelled) | Priftin (sanofi-aventis U.S. LLC) | Film-coated tablet (oral) | Not listed in the data compiled for this report |
Safety Considerations
- Contraindication-related conditions (from the knowledge graph, not label text): inherited porphyria, porphyrin metabolism disease, porphyria, liver disease, gallbladder disease, substance abuse/dependence, hyperbilirubinemia, hereditary hyperbilirubinemia, Gilbert syndrome, Clostridium difficile colitis, perinatal necrotizing enterocolitis.
- Drug Interactions: 100 interactions were identified. Examples:
- Major: eliglustat, naldemedine.
- Moderate: rabeprazole, corticosteroids (hydrocortisone, dexamethasone, betamethasone, triamcinolone), vitamin D analogues (cholecalciferol, calcifediol, calcitriol), antidiabetics (pioglitazone, saxagliptin, linagliptin, glimepiride, chlorpropamide), aprepitant, metronidazole, clarithromycin, dronabinol.
- Antiretroviral interactions: rifapentine is a CYP3A4 inducer, so interactions with dolutegravir, bictegravir, tenofovir alafenamide and other antiretrovirals are a central concern for the HIV-related extension. Dedicated pharmacokinetic studies are under way.
- Hepatotoxicity: published work on rifapentine plus isoniazid in people with HIV examines drug-induced liver injury, but one such paper (PMID 33758553) has been retracted and should not be relied upon.
Package insert warnings and contraindications were not available. Please refer to the package insert for full safety information.
Conclusion and Next Steps
Decision: Hold (for leprosy as the primary prediction)
Rationale:
- Leprosy is biologically plausible, but there are no registered trials. The key household-contact publications have not been verified as controlled studies, so the evidence level cannot be raised above L3 yet.
- Lower-ranked predictions (breast carcinoma, Prinzmetal angina, neuroretinitis, vestibular neuronitis, neuritis types, dermatofibrosarcoma protuberans) have no meaningful supporting data, and rheumatoid arthritis evidence concerns TB prophylaxis in RA patients rather than RA treatment. All remain on Hold.
- The HIV-associated TB extension has Phase 3 support and could Proceed with Guardrails. It is a population extension of the original TB indication, not a new disease target.
To proceed, the following is needed:
- Full-text review of PMIDs 37195940 and 37585641 to confirm design, phase and results for leprosy prophylaxis.
- Clinical trials of rifapentine in leprosy treatment or prophylaxis.
- Mechanism-of-action data from DrugBank.
- Package insert warnings and contraindications from the FDA.
- Clarification of US regulatory status, since the only NDA on record is cancelled.
- A drug-interaction management plan, especially for antiretrovirals and the major-level interactions.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.