Iloperidone
| Evidence Level: L5 | Predicted Indications: 9 |
Table of Contents
Iloperidone: Retinal dystrophy with or without extraocular anomalies
One-Sentence Summary
Iloperidone is an atypical antipsychotic originally used to treat schizophrenia. Currently 18 publications support this direction, including a double-blind, placebo-controlled study, but no clinical trials are registered in the data compiled for this report.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Retinal dystrophy with or without extraocular anomalies |
| TxGNN Prediction Score | 1.0000 |
| Evidence Level | L5 (provisional, see note below) |
| India Market Status | Listed in a compiled Indian medicine price dataset (at least 20) – CDSCO approval status is not included in this data |
| Number of Listed Products | at least 20 |
| Recommended Decision | Proceed with Guardrails |
Note: The L1 level rests on the titles of the literature. The pivotal study is described as a phase 3 randomized, double-blind, placebo-controlled study, but its results and a second completed Phase 3 trial have not been verified, so the level may be overstated.
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available. Based on known class pharmacology, iloperidone is an atypical antipsychotic that blocks dopamine D2 and serotonin 5-HT2A receptors. It is a benzisoxazole, structurally related to risperidone.
Schizophrenia and bipolar mania share psychotic and behavioural symptoms, and other atypical antipsychotics are already used for acute mania. This makes it mechanistically plausible that iloperidone works in mania too.
The literature supports this. A 2024 phase 3, randomized, double-blind, placebo-controlled study tested iloperidone (up to 24 mg/day) against placebo over 4 weeks in adults with bipolar mania. Reviews from 2024 and 2025 also describe a new US indication for acute treatment of bipolar I disorder mania. An earlier open trial in mixed episodes (2017) points the same way.
Clinical Trial Evidence
Currently no related clinical trials are registered in the data compiled for this report.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 38236020 | 2024 | RCT | J Clin Psychiatry | Phase 3 double-blind, placebo-controlled study of iloperidone (up to 24 mg/day) in adults with bipolar mania over 4 weeks; the primary endpoint was change in Young Mania Rating Scale score |
| 39800949 | 2025 | Review | Ann Pharmacother | Evaluates iloperidone efficacy for mania in bipolar I disorder and its safety profile (QTc prolongation, orthostatic hypotension, metabolic effects) |
| 39008105 | 2024 | Review | Med Lett Drugs Ther | Note on iloperidone (Fanapt) and its new bipolar disorder indication |
| 39126643 | 2024 | Review | Expert Opin Drug Saf | Safety review of atypical antipsychotics, QTc interval and torsades de pointes |
| 42213400 | 2026 | Review | Clin Drug Investig | Milsaperidone, an active metabolite of iloperidone; iloperidone approved in the USA for schizophrenia (2009) and acute bipolar I disorder (2024) |
| 22900950 | 2012 | Systematic review | CNS Drugs | Body weight and metabolic adverse effects of asenapine, iloperidone, lurasidone and paliperidone in schizophrenia and bipolar disorder |
| 22849428 | 2012 | Review | Expert Opin Pharmacother | Overview of iloperidone, asenapine and lurasidone |
| 27372312 | 2016 | Review | CNS Drugs | Incidence, mechanisms and management of antipsychotic-induced somnolence |
| 30187288 | 2018 | Review | Drugs Aging | Newer atypical antipsychotics for bipolar disorder, with considerations for older patients |
| 28817490 | 2017 | Open trial | J Clin Psychopharmacol | Open trial of iloperidone for mixed episodes in bipolar disorder |
India Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| Registration No. 113558 | Ilofast 6mg Tablet (Zydus Cadila) | Strip of 30 tablets | Not stated |
| Registration No. 112404 | Ilofast 8mg Tablet (Zydus Cadila) | Strip of 30 tablets | Not stated |
| Registration No. 113599 | Ilobril 8mg Tablet (Torrent Pharmaceuticals Ltd) | Strip of 10 tablets | Not stated |
| Registration No. 112311 | Iiosure 6mg Tablet (Sun Pharmaceutical Industries Ltd) | Strip of 10 tablets | Not stated |
| Registration No. 112895 | Ilopride 6mg Tablet (Intas Pharmaceuticals Ltd) | Strip of 10 tablets | Not stated |
There are 20 valid single-ingredient registrations in total. All are oral tablets, and none has approved indication text on record.
Safety Considerations
- Contraindications and disease-level cautions (from the knowledge graph, not label text): the data link iloperidone to caution in the following conditions.
- Cardiovascular: long QT syndrome (including familial), torsades de pointes, sudden cardiac arrest, heart conduction disease, myocardial infarction, orthostatic hypotension, multiple system atrophy, postural orthostatic tachycardia syndrome
- Blood: neutropenia, agranulocytosis, leukopenia
- Metabolic: diabetes mellitus, diabetic ketoacidosis, hyperglycemia, obesity, potassium deficiency
- Neurological and movement: epilepsy, Alzheimer disease, neuroleptic malignant syndrome, tardive dyskinesia
- Other: liver disease, gallbladder disease, female breast carcinoma, priapism
- Drug Interactions: 239 interactions were found. Major ones include bupropion, morphine and clarithromycin. Moderate ones include antidiabetic agents (metformin, pioglitazone, acarbose, alogliptin, canagliflozin, chlorpropamide, albiglutide), anticholinergic agents (atropine, hyoscyamine, glycopyrronium), epinephrine, famotidine, loperamide and lorcaserin.
- Literature-highlighted risks: QTc prolongation, orthostatic hypotension, metabolic and weight effects, somnolence, and a raised uric acid signal in the bipolar mania trial.
Please also refer to the package insert for full warnings and contraindications.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: A 2024 phase 3 placebo-controlled study, supported by reviews describing a new US bipolar I mania indication, makes this prediction clinically credible. However, the evidence level has not been confirmed against trial registry records, and the safety burden is considerable (QTc, metabolic effects, many drug interactions).
To proceed, the following is needed:
- Verification of the pivotal trial’s phase, design and results, and identification of a second confirmatory trial
- Mechanism of action data from DrugBank
- Indication text and warnings from the India package insert (CDSCO-approved labelling)
- A safety monitoring plan covering QTc, metabolic parameters, orthostatic hypotension and interacting medicines
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.