Atovaquone
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Atovaquone: From Malaria and Pneumocystosis to Leprosy
One-Sentence Summary
Atovaquone is an antiparasitic and anti-Pneumocystis drug, originally used to treat Plasmodium falciparum malaria and pneumocystosis. The TxGNN model predicts it may be effective for leprosy, but there are 0 clinical trials and 1 publication (unrelated to atovaquone in leprosy), so this prediction rests on computation alone.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Plasmodium falciparum malaria, malaria, pneumocystosis (the Singapore licence has no approved indication text recorded) |
| Predicted New Indication | Leprosy |
| TxGNN Prediction Score | 94.24% |
| Evidence Level | L5 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 1 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available. Based on known information, atovaquone is an antiparasitic agent whose efficacy in malaria and pneumocystosis is established. Its approved Singapore product is MALARONE, an atovaquone-containing product.
The data compiled for this report did not establish a direct mechanistic link between atovaquone and leprosy. Leprosy is a bacterial (mycobacterial) infection, whereas atovaquone's established uses are against protozoa and Pneumocystis. The high TxGNN score appears to reflect network proximity, since both are anti-infective, rather than clinical or experimental evidence. The only paper retrieved concerns clofazimine, a leprosy drug, for Babesia microti infection. It mentions atovaquone only as a drug that babesiosis can become resistant to, so it does not support atovaquone for leprosy.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 32310272 | 2020 | Case report/Review | The Journal of Infectious Diseases | Tests clofazimine (a leprosy and drug-resistant tuberculosis antibiotic) against Babesia microti, including infections resistant to atovaquone. It does not evaluate atovaquone for leprosy. |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN09761P | MALARONE TABLET | Tablet, film coated | Not recorded in the data compiled for this report |
Safety Considerations
- Disease associations flagged in the knowledge graph (not label text): liver failure, liver disease, gallbladder disease, hyperglycaemia, chronic diarrhoeal disease.
- Drug Interactions: 100 interactions were identified. Those rated Moderate include metoclopramide, naltrexone, tetracycline and picosulfuric acid. Many others have an unrated severity, including proton pump inhibitors (omeprazole, pantoprazole, lansoprazole), metformin, morphine, corticosteroids (prednisone, prednisolone, hydrocortisone, triamcinolone), vancomycin and amphotericin B.
Please refer to the package insert for full warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction is computational only (evidence level L5). There are no registered trials and no relevant literature, and no mechanistic link between atovaquone and leprosy has been shown. The high score most likely reflects the drug's anti-infective class rather than real efficacy.
To proceed, the following is needed:
- Mechanism of action data for atovaquone
- In vitro activity data against Mycobacterium leprae, or preclinical studies, to establish biological plausibility
- Package insert warnings and contraindications from the Singapore regulator (HSA) to allow safety screening
- Any clinical or observational data on atovaquone in leprosy; none has been found
Other predicted indications to consider: Among the other predictions, toxoplasmosis (Phase 2 randomized trial in toxoplasmic encephalitis, Level L2) and ocular toxoplasmosis (small clinical series and case reports, Level L3) have the most supporting evidence. Both are already partly established alternative uses and would suit a separate evaluation. The nocardiosis literature points to a negative signal: nocardial infections increased in the era of atovaquone prophylaxis. The remaining predictions (facial nerve palsy due to herpes zoster, acne, and the myiasis group) have no supporting evidence.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.