Naltrexone
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Naltrexone: From Substance Dependence and Obesity to Hypervitaminosis
One-Sentence Summary
Naltrexone is an opioid receptor antagonist originally used for substance abuse/dependence and obesity (including monogenic obesity). The TxGNN model predicts it may be effective for hypervitaminosis, but this is a model prediction only, with 0 clinical trials and 0 publications supporting this direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Substance abuse/dependence, obesity disorder, monogenic obesity (the Singapore licence records contain no approved indication text) |
| Predicted New Indication | Hypervitaminosis |
| TxGNN Prediction Score | 98.66% |
| Evidence Level | L5 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 2 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the data compiled for this report. Based on known pharmacology, naltrexone is a mu-opioid receptor antagonist. It is used for substance dependence and, in combination with bupropion, for obesity.
For hypervitaminosis, no mechanistic link was identified. Naltrexone has no known relationship to vitamin metabolism or toxicity, and no trials or literature support this indication. The high score (98.66%) should be read as a model output only, not as evidence of benefit. The rank of 13,132 for this prediction also indicates the score alone is not very discriminating.
Other predictions for this drug were reviewed. Most (for example craniofacial malformations, hypospadias and bridged sella turcica) have no plausible mechanism. Two have a weak indirect rationale:
- Proximal 16p11.2 microdeletion syndrome (score 98.13%): the deletion is linked to hyperphagia and severe obesity, which overlaps with naltrexone's obesity use. This is speculative, and no specific data exist.
- Restless legs syndrome (score 92.20%): the opioid system is implicated, but opioid antagonism would be expected to worsen rather than improve symptoms. The retrieved literature does not evaluate naltrexone for this condition.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
Currently no related literature available for hypervitaminosis.
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN10002P | NARPAN TABLET 50 mg | Tablet | Not stated in the licence record |
| SIN16411P | CONTRAVE PROLONGED RELEASE TABLET 8MG/90MG | Film-coated extended-release tablet | Not stated in the licence record |
Safety Considerations
- Contraindication signals from the knowledge graph (not label text): liver failure, acute liver failure, hepatitis and liver disease; impaired renal function; respiratory failure and COPD; epilepsy; pancreatitis; gallbladder disease; hypothyroidism and myxedema; adrenal insufficiency (including Addison disease and congenital adrenal hyperplasia); anxiety and dysthymic disorders; benign prostatic hyperplasia; hypotension; chronic diarrhoeal disease; paralytic ileus.
- Drug Interactions: 100 interactions were found in total. The main ones listed are:
- Major: fentanyl, codeine, dihydrocodeine, tramadol (opioid drugs, whose effects are blocked by naltrexone).
- Moderate examples: abacavir, lamivudine, zidovudine, isotretinoin, acitretin, acetaminophen, ibuprofen, ketorolac, ethanol, abemaciclib, abiraterone and afatinib.
Please also refer to the package insert for label-based warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction rests on a model score alone. There are no trials or publications, and no plausible mechanism links an opioid antagonist to hypervitaminosis (evidence level L5).
To proceed, the following is needed:
- A mechanistic rationale showing how naltrexone could affect vitamin handling or toxicity
- Detailed mechanism of action data (MOA)
- Package insert warnings and contraindications from the HSA website, plus approved indication text for the Singapore licences
- If a lead candidate is wanted, evaluate better-supported predictions first (such as 16p11.2 microdeletion syndrome, which overlaps with the obesity use) through preclinical or literature review
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.