Rifampicin
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
Rifampicin: From Pulmonary Tuberculosis to Conjunctivitis
One-Sentence Summary
Rifampicin is an RNA polymerase-inhibiting antibiotic, originally used to treat pulmonary tuberculosis. The TxGNN model predicts it may be effective for conjunctivitis (the top-ranked prediction), but there are no registered clinical trials and the literature (19 publications) consists mainly of microbiology susceptibility surveys, case reports and old trachoma and chlamydial eye infection studies from the 1970s.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Pulmonary tuberculosis (from the TxGNN knowledge graph; the Singapore licence records contain no indication text) |
| Predicted New Indication | Conjunctivitis |
| TxGNN Prediction Score | 99.95% |
| Evidence Level | L4 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 2 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on known pharmacology, rifampicin is a broad-spectrum antibiotic that inhibits bacterial RNA polymerase. It is active against Gram-positive bacteria, Chlamydia and some other ocular pathogens.
Infectious conjunctivitis is commonly caused by bacteria such as Staphylococcus, Streptococcus and Chlamydia trachomatis. Because rifampicin acts against several of these organisms, antibacterial activity in infectious conjunctivitis is plausible. The old trials used topical 1% rifampicin ointment, whereas the Singapore products are oral capsules, so route compatibility has not been established.
The other predictions are weaker:
- Hidradenitis suppurativa / acne inversa (listed under acne): guidelines mention rifampicin combined with clindamycin. This is indirect evidence, because it concerns a different disease from acne vulgaris. There is also a prospective European cohort study (PMID 33484766).
- Rheumatoid arthritis: small clinical studies from 1988 to 1993 showed modest or inconsistent benefit. The only registered trial is a Phase 1 drug interaction study.
- HIV infection (and the feline and simian immunodeficiency entries): rifampicin has no known direct anti-HIV activity. The trials concern HIV-TB co-infection, where rifampicin treats tuberculosis.
- Multiple endocrine neoplasia, a rare neurodevelopmental disorder and acute contagious conjunctivitis: no trials or literature, so these are model predictions only.
Clinical Trial Evidence
Currently no related clinical trials registered for conjunctivitis.
For reference, trials registered under lower-ranked predictions do not test the predicted indication directly:
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00933790 | Phase 3 | Completed | 331 | Daily vs intermittent TB chemotherapy in HIV-TB patients (tests TB, not HIV) |
| NCT00495326 | Phase 2/3 | Completed | 570 | Nevirapine- vs efavirenz-based ART in HIV-TB patients on rifampicin |
| NCT03927313 | Phase 2 | Completed | 52 | High-dose rifampicin plus linezolid in HIV-associated TB meningitis (safety) |
| NCT01336218 | Phase 1 | Completed | 15 | Fostamatinib and rifampicin drug interaction in healthy subjects; no efficacy data for rheumatoid arthritis |
Literature Evidence
Literature for the top prediction (conjunctivitis), prioritised by study design:
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 1096630 | 1975 | Controlled clinical trial | Am J Ophthalmol | 1% rifampicin vs 1% tetracycline ointment vs boric acid control in endemic trachoma in Tunisian schoolchildren (twice daily, 10 weeks) |
| 322700 | 1977 | Open trial | Br J Ophthalmol | 63 patients with chlamydial eye infection: 1% rifampicin ointment vs chloramphenicol; 3 weeks was insufficient, but 6 to 7 weeks gave about 90% clinical and microbiological cure |
| 33457332 | 2020 | Susceptibility study | Adv Biomed Res | Bacterial causes and antibiotic susceptibility in conjunctivitis patients in Iran |
| 8363150 | 1993 | Microbiology study | An Esp Pediatr | Neonatal conjunctivitis pathogens and antibiotic sensitivity |
| 21191558 | 2010 | Susceptibility study | Rev Esp Quimioter | Antibiotic susceptibility of Corynebacterium macginleyi strains causing conjunctivitis |
| 3191080 | 1988 | Case report | Br J Ophthalmol | Marginal corneal abscess in adult chlamydial ophthalmia |
| 39336466 | 2024 | Case report | Medicina (Kaunas) | Parinaud oculoglandular syndrome with Bartonella DNA detected in cornea and conjunctiva |
| 5005929 | 1971 | Review | Ann Ophthalmol | Overview of rifampicin (no abstract available) |
| 1247775 | 1976 | Report | Br Med J | Ocular toxicity due to rifampicin |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN16652P | ROYCE RIFAMPICIN CAPSULE 150MG | Capsule | Not stated in the registration record |
| SIN16653P | ROYCE RIFAMPICIN CAPSULE 300MG | Capsule | Not stated in the registration record |
Both are valid single-ingredient oral products from Royce Pharma Manufacturing Sdn. Bhd. No topical or ophthalmic formulation is registered.
Safety Considerations
- Contraindications and disease associations (from the knowledge graph, not label text): liver failure, acute liver failure, hepatitis and other liver disease; porphyria; gallbladder disease; blood disorders (thrombocytopenia, neutropenia, agranulocytosis, pancytopenia, aplastic anaemia, anaemia); diabetes mellitus and diabetic ketoacidosis; gout; peripheral neuropathy; substance abuse/dependence; slow acetylator status; non-infectious meningitis; and anxiety, neurotic and dysthymic disorders.
- Drug Interactions: 100 interactions were found, and the 20 listed in the data are all moderate. They include rabeprazole, omeprazole, doxycycline, clarithromycin, metronidazole, metformin, pioglitazone, canagliflozin, chlorpropamide, bupropion, aprepitant, morphine, and corticosteroids (hydrocortisone, dexamethasone, betamethasone, triamcinolone) and vitamin D analogues (cholecalciferol, calcifediol, calcitriol). Rifampicin is a potent enzyme inducer and lowers the exposure of many co-administered drugs, including antiretrovirals and corticosteroids.
- Ocular toxicity: the literature includes reports of ocular toxicity due to rifampicin (PMID 1247775, 1260294).
Please refer to the package insert for warnings and precautions; label warning text was not available in the data compiled for this report.
Conclusion and Next Steps
Decision: Hold
Rationale: The conjunctivitis prediction is biologically plausible, but the evidence is limited to old topical-ointment studies, susceptibility surveys and case reports (L4), with no registered or modern controlled trials. The available Singapore products are oral only. Other predictions have either no evidence or only indirect evidence (HIV-TB co-infection, hidradenitis suppurativa, rheumatoid arthritis). RA and HIV are flagged as research questions rather than repurposing candidates.
To proceed, the following is needed:
- HSA package insert warnings and contraindications (currently a blocking data gap for safety screening)
- Mechanism of action data from DrugBank
- A comparison against current standard topical antibiotics for bacterial conjunctivitis and trachoma
- Assessment of whether an ophthalmic formulation is feasible, since only oral capsules are registered in Singapore
- A modern, controlled trial or a systematic review of rifampicin in chlamydial and other bacterial eye infections
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.