Fluphenazine
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
- Fluphenazine
- Fluphenazine: From Antipsychotic Use to Retinal Dystrophy (With or Without Extraocular Anomalies)
Fluphenazine: From Antipsychotic Use to Retinal Dystrophy (With or Without Extraocular Anomalies)
One-Sentence Summary
Fluphenazine is a phenothiazine antipsychotic that acts as a dopamine D2 antagonist and is marketed in the US in oral, injectable and elixir forms. The TxGNN model predicts it may be effective for retinal dystrophy with or without extraocular anomalies, but there are 0 clinical trials and no literature on fluphenazine for this condition. This is a graph-based prediction only, and phenothiazines are known to cause retinal toxicity, which argues against this use.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Antipsychotic use (indication text is not provided in the US license data) |
| Predicted New Indication | Retinal dystrophy with or without extraocular anomalies |
| TxGNN Prediction Score | 99.99% (model rank 321) |
| Evidence Level | L5 |
| US Market Status | ✓ Marketed |
| Number of NDAs | 20 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data is not available in the Evidence Pack. Fluphenazine is a high-potency phenothiazine and a D2 dopamine receptor antagonist.
The review found no plausible mechanistic link between D2 antagonism and the genetic or structural pathology of retinal dystrophy. The high TxGNN score (0.9999) reflects only a pattern in the knowledge graph, not biological or clinical support.
Phenothiazines are also known to cause retinal toxicity (pigmentary retinopathy). This is a reason for caution, not support for the prediction.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
The 15 retrieved publications were matched on disease keywords (orbital, extraocular and congenital eye disorders). None of them studies fluphenazine or any phenothiazine in retinal dystrophy. The 10 below are the closest in topic, and all are background reading only.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 9416661 | 1997 | Review | Semin Ultrasound CT MR | Orbital infections, mainly sinusitis-related; imaging and clinical signs |
| 20127583 | 2010 | Review | Semin Neurol | Systematic approach to evaluating diplopia |
| 38321238 | 2024 | Review | Pediatr Radiol | Differential diagnosis and imaging of pediatric ocular pathologies |
| 38249493 | 2023 | Review | Taiwan J Ophthalmol | Congenital anomalies of lens shape |
| 22241537 | 2012 | Review | Klin Monbl Augenheilkd | Congenital ptosis and its associated findings |
| 7035111 | 1981 | Review | Doc Ophthalmol | Wagner-Stickler syndrome complex (vitreoretinal degeneration) |
| 30196776 | 2018 | Review | J Binocul Vis Ocul Motil | Ophthalmoplegia and congenital cranial dysinnervation disorders |
| 24932988 | 2014 | Review | Am J Ophthalmol | Pathogenesis and treatment of maculopathy with cavitary optic disc anomalies |
| 33806565 | 2021 | Cohort | Int J Mol Sci | Optic nerve head and retinal abnormalities in congenital fibrosis of the extraocular muscles |
| 109006 | 1979 | Case report | Am J Ophthalmol | Two cases of unilateral cryptophthalmia |
US Market Information
Of 20 authorizations, the 5 listed in the Evidence Pack are shown below. All are generic (ANDA) tablets.
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ANDA218173 | Fluphenazine Hydrochloride (Alembic) | Film-coated tablet | — |
| ANDA213647 | Fluphenazine Hydrochloride (Amneal) | Film-coated tablet | — |
| ANDA218055 | Fluphenazine Hydrochloride (Aurobindo) | Tablet | — |
| ANDA214534 | Fluphenazine Hydrochloride (American Health Packaging) | Film-coated tablet | — |
| ANDA217410 | Fluphenazine Hydrochloride (Ajanta) | Tablet | — |
Other US dosage forms for this drug are injection solution and elixir.
Safety Considerations
- Retinal toxicity: Phenothiazines are known to cause pigmentary retinopathy. This directly conflicts with use in a retinal disease.
Please refer to the package insert for other safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction rests on the model score alone (L5). There are no trials, no fluphenazine-specific literature and no plausible mechanism. The known retinal toxicity of phenothiazines argues against this indication.
To proceed, the following is needed:
- A defined mechanistic hypothesis that addresses the retinal toxicity concern, backed by preclinical data
- Full package insert warnings and contraindications
- Mechanism-of-action data from DrugBank
Note on other predictions: Of the 10 predicted indications, only rank 10, manic bipolar affective disorder (score 99.98%), has a plausible mechanism. Dopamine antagonism underlies the antimanic effect of the antipsychotic class, and class-level reviews and retrospective data support long-acting injectable antipsychotics in bipolar disorder. Fluphenazine-specific evidence is limited to one two-patient case report, so this is a class-effect inference. It is rated L4 and best treated as a research question, and it would be the better candidate for a follow-up report.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.