Iodine
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Iodine: From Iodinated Contrast Imaging to Sjögren Syndrome
One-Sentence Summary
Iodine is marketed in Singapore as part of iodinated contrast injections (Iomeron, Ultravist, Omnipaque). The TxGNN model predicts it may be effective for Sjögren syndrome, but no clinical trials and only 20 publications support this, and those describe associations, adverse effects, or diagnostic use rather than treatment. The one direction with real clinical-trial activity is keratitis (povidone-iodine), with 3 clinical trials and 19 publications.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not available (the registration records contain no approved indication text) |
| Predicted New Indication | Sjögren syndrome |
| TxGNN Prediction Score | 94.09% |
| Evidence Level | L5 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 7 |
| Recommended Decision | Hold |
The top-ranked prediction is weakly supported. Among the other predictions, keratitis has the strongest evidence (rated L1 by the data compiled for this report, to be treated conservatively; see below).
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available. All seven Singapore registrations are iodinated injections (iomeprol, iopamidol-type and iohexol-type contrast products), whose original role is diagnostic imaging, not treatment.
For Sjögren syndrome, the literature does not support a therapeutic link. It shows that Sjögren syndrome co-occurs with autoimmune thyroid disease, that the sodium-iodide symporter (NIS), which takes up iodine, is expressed in both thyroid and salivary glands and is discussed as a possible shared autoantigen, and that radioactive iodine can cause salivary gland inflammation resembling or complicating Sjögren syndrome. Iodine is therefore more plausibly a risk factor or a diagnostic agent (sialography contrast) than a treatment. The high model score is not backed by clinical evidence.
The more credible repurposing signal is keratitis. Povidone-iodine (an iodine complex) releases free iodine and has bactericidal, fungicidal, virucidal and amoebicidal activity, and it is already used in ophthalmology for antisepsis. This gives a direct mechanistic rationale for infectious corneal ulcers. Note that it concerns a topical antiseptic form, not the injectable contrast products registered in Singapore.
Other predictions (rank 2 to 10) have little or no support:
- Acne (93.1%): only indirect antimicrobial rationale and an uncontrolled pilot of PVP-iodine hydrogel in infective dermatoses (L4).
- Recurrent corneal erosion (90.7%): a single 1964 paper (L4).
- Lacrimal gland neoplasm (89.4%): literature mainly reports lacrimal damage caused by radioactive iodine, a safety signal (L4).
- Lacrimal gland prolapse, vulvar inverted follicular keratosis: no evidence.
- Seborrheic keratosis, fetal erythroblastosis, peptic esophagitis: literature is diagnostic or adverse-effect only (L5).
Clinical Trial Evidence
No clinical trials are registered for the top prediction (Sjögren syndrome). The only registered trials are for the rank 7 prediction, keratitis (TxGNN score 89.70%), shown below for reference:
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00516399 | Phase 3 | Terminated | 78 | 1.25% povidone-iodine ophthalmic solution vs an antifungal antibiotic in small to medium fungal corneal ulcers; terminated early, so likely underpowered and the outcome needs checking |
| NCT00386958 | Phase 2 | Completed | 172 | Povidone-iodine as an inexpensive broad-spectrum treatment for bacterial corneal ulcers |
| NCT03484507 | Phase 2 | Completed | 49 | Pilot in Acanthamoeba keratitis: chlorhexidine alone vs chlorhexidine plus povidone-iodine, then re-randomisation to corticosteroid timing or placebo |
Results for these trials were not included in the data compiled for this report.
Literature Evidence
For the top prediction (Sjögren syndrome), the most relevant publications are listed below. None is a randomised trial of treatment.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 41516079 | 2025 | In silico epitope prediction | Int J Mol Sci | Computational study of NIS epitopes as a possible link between Sjögren syndrome and Hashimoto thyroiditis |
| 7485204 | 1995 | Cohort/Observational | Am J Med | Prevalence of autoimmune thyroid disease in primary Sjögren syndrome |
| 35817018 | 2023 | Case/Clinical management report | ORL | Sialendoscopy for chronic sialadenitis due to Sjögren syndrome and radioactive iodine therapy |
| 24899999 | 2011 | Diagnostic study | Nucl Med Mol Imaging | Salivary gland scintigraphy comparing Sjögren syndrome with post-radioiodine salivary dysfunction |
| 28059621 | 2017 | Review | Neuroradiol J | Imaging findings of sialadenitis |
For keratitis, the strongest publications are:
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 40728038 | 2025 | Network meta-analysis | Cochrane Database Syst Rev | Topical antibiotics for bacterial keratitis |
| 32959365 | 2020 | Systematic review | Cochrane Database Syst Rev | Interventions for preventing ophthalmia neonatorum (includes antiseptics) |
| 37944600 | 2024 | Review | Surv Ophthalmol | Povidone-iodine has bactericidal, fungicidal and virucidal action and is widely used in ophthalmology |
| 28984794 | 2018 | Review | Curr Opin Ophthalmol | Use of povidone-iodine in ophthalmology, including prophylaxis of endophthalmitis |
| 12605049 | 2003 | Experimental animal study | Cornea | 1% povidone-iodine and polyhexamethylene biguanide in experimental Aspergillus keratitis |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN08462P | IOMERON 350 INJECTION 350 mg/ml | Injection | Not stated in the registration record |
| SIN08457P | IOMERON 300 INJECTION 300 mg/ml | Injection | Not stated in the registration record |
| SIN08458P | IOMERON 400 INJECTION 400 mg/ml | Injection | Not stated in the registration record |
| SIN05845P | ULTRAVIST 370 INJECTION 370 mg Iodine/ml | Injection | Not stated in the registration record |
| SIN05841P | ULTRAVIST 300 INJECTION 300 mg Iodine/ml | Injection | Not stated in the registration record |
Two more registrations (OMNIPAQUE 350 and 300 mg I/ml, SIN05923P and SIN05924P) are also valid. All seven are single-ingredient injectable products, and none is cancelled.
Safety Considerations
- Drug Interactions (3 moderate-level interactions): Iodide I-131, Iodide I-123 and lithium carbonate. Lithium combined with iodine may add to thyroid-suppressing effects.
- Conditions flagged in the knowledge graph (contraindication links in the TxGNN knowledge graph, not label text): epilepsy, kidney disease, liver disease, gallbladder disease, thyroid conditions (hypothyroidism, myxedema, congenital hypothyroidism, Hashimoto thyroiditis), blood disorders (thrombocytopenia, neutropenia, agranulocytosis), respiratory conditions (bronchitis, respiratory failure, pulmonary tuberculosis), heart block, pyoureter and hypocomplementemic urticarial vasculitis. These need confirmation against the product labels.
- Safety signals in the literature: radioactive iodine causes salivary and lacrimal gland dysfunction and nasolacrimal duct obstruction, and iodinated contrast used in amniography was linked to fetal thyroid hyperplasia. These argue against a therapeutic use in Sjögren syndrome and lacrimal conditions.
Please refer to the package insert for label warnings and contraindications, which were not available for this report.
Conclusion and Next Steps
Decision: Hold
Rationale: The top prediction (Sjögren syndrome) is supported only by association and adverse-effect literature, with no trials, so the high model score is not backed by clinical evidence. The injectable contrast products registered in Singapore are also not the form relevant to the best-supported signal (topical povidone-iodine in infectious keratitis), which remains a research question rather than a ready candidate.
To proceed, the following is needed:
- HSA package insert warnings and contraindications (a blocking gap for safety screening)
- Mechanism of action data from DrugBank
- Outcome data from NCT00516399 (terminated Phase 3), NCT00386958 and NCT03484507 for keratitis
- A decision on whether povidone-iodine, a topical ophthalmic antiseptic, is the product to evaluate, since it is distinct from the registered injectable contrast agents, plus its registration status in Singapore
- For Sjögren syndrome, any controlled evidence of therapeutic benefit, which is currently absent
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.