Dorzolamide
| Evidence Level: L5 | Predicted Indications: 7 |
Table of Contents
Dorzolamide: Hypotrichosis simplex of the scalp
One-Sentence Summary
Dorzolamide is a topical carbonic anhydrase inhibitor, originally used to lower eye pressure in open-angle glaucoma and ocular hypertension. The TxGNN model’s top-ranked prediction is hypotrichosis simplex of the scalp, but no clinical trials and no publications specifically support it. Of the ten predictions reviewed, only open-angle glaucoma has strong evidence (34 registered trials), and that is the drug’s existing approved use rather than a new one.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Hypotrichosis simplex of the scalp |
| TxGNN Prediction Score | 0.9995 |
| Evidence Level | L5 |
| Australia Market Status | Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data |
| Number of PBS Items | 1 (valid: 1) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the compiled data. Based on known pharmacology, dorzolamide inhibits carbonic anhydrase II in the ciliary processes. This reduces aqueous humour formation and lowers intraocular pressure. Pharmacology data also lists activity at carbonic anhydrase 1, 7, 12 and 14.
Other predictions reviewed
| Predicted Indication | Score | Evidence Level | Assessment |
|---|---|---|---|
| Congenital hypotrichosis milia | 0.9994 | L5 | No identifiable mechanism. No evidence. |
| Alopecia | 0.9990 | L5 | No credible mechanism. The only paper is a veterinary case report on a dog, which is not evidence of efficacy. |
| Diffuse alopecia areata | 0.9990 | L5 | Autoimmune condition with no established role for carbonic anhydrase inhibition. No evidence. |
| Congestive heart failure | 0.9961 | L5 | Loose rationale from systemic inhibitors; topical exposure is low. Papers cover interactions and prescribing context only. |
| Acute pulmonary heart disease | 0.9953 | L5 | Speculative link only. No evidence. |
| Respiratory failure | 0.9927 | L5 | Systemic inhibitors can stimulate respiration, but ocular dosing is unlikely to reach relevant levels. No evidence. |
Clinical Trial Evidence
Currently no related clinical trials are registered for primary hereditary glaucoma.
The only substantial trial evidence relates to open-angle glaucoma, which is the drug’s existing indication. Up to 10 of the 34 registered trials are shown below. I selected completed Phase 3 trials first, then larger Phase 4 trials. No ANZCTR identifiers were included in the compiled data.
| Trial Number | Phase | Status | Enrolment | Key Findings |
|---|---|---|---|---|
| NCT00314171 | Phase 3 | Completed | 437 | Safety and efficacy of a glaucoma therapy in open-angle glaucoma or ocular hypertension (the title is truncated, so dorzolamide’s exact role should be verified) |
| NCT00108017 | Phase 3 | Completed | 330 | 24-hour pressure-lowering effect of dorzolamide 2%/timolol 0.5% combination |
| NCT00878917 | Phase 3 | Completed | 32 | Crossover equivalence study of dorzolamide 2% eye drops against a reference solution |
| NCT00546286 | Phase 3 | Completed | 170 | Open-label study of dorzolamide-timolol as first-line therapy in untreated patients |
| NCT00576342 | Phase 3 | Completed | 129 | Single-drop patient comfort preference study |
| NCT03257813 | Phase 3 | Completed | 60 | Non-inferiority of a dorzolamide-containing product (PRO-122) against a comparator |
| NCT00991822 | Phase 2/3 | Completed | 160 | Dorzolamide vs timolol effect on optic disc blood flow |
| NCT02325518 | Phase 4 | Completed | 218 | Brinzolamide/timolol vs dorzolamide/timolol fixed combination |
| NCT00675207 | Phase 4 | Completed | 120 | Brimonidine, dorzolamide and brinzolamide added to prostaglandin analogues |
| NCT01527682 | Phase 2 | Completed | 37 | Latanoprost and dorzolamide in paediatric glaucoma refractory to surgery |
Literature Evidence
No literature is available for primary hereditary glaucoma. The following publications relate to open-angle glaucoma, the existing indication.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 26526633 | 2016 | Systematic review / network meta-analysis | Ophthalmology | Comparative effectiveness of first-line medications for primary open-angle glaucoma |
| 17943780 | 2007 | Cochrane systematic review | Cochrane Database Syst Rev | Medical interventions for primary open-angle glaucoma and ocular hypertension |
| 39677168 | 2024 | RCT (Phase 3) | Cureus | Brinzolamide/timolol vs dorzolamide/timolol in Indian patients |
| 19365194 | 2009 | RCT | J Glaucoma | Brinzolamide/timolol vs dorzolamide/timolol after a change in therapy |
| 16968583 | 2006 | RCT | Curr Med Res Opin | Travoprost vs dorzolamide/timolol fixed combination |
| 32106236 | 2020 | Meta-analysis | PLoS One | Latanoprost/timolol vs other fixed combinations |
| 9143858 | 1997 | Review | Drugs Aging | Dorzolamide pharmacology; lowers intraocular pressure by about 4 to 6 mmHg at peak |
| 11200308 | 2000 | Review | Drugs Aging | Dorzolamide/timolol combination; additive effect with different mechanisms |
| 12204712 | 2002 | Review | Surv Ophthalmol | Latanoprost vs combined timolol and dorzolamide |
| 40261315 | 2025 | Review | Med Lett Drugs Ther | Overview of drugs for open-angle glaucoma |
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 14524K (as listed in the data) | Trusopt | Eye drops 20 mg (as hydrochloride) per mL, 5 mL | Not recorded in the data compiled for this report |
Safety Considerations
- Contraindications flagged in the knowledge graph (these are graph associations, not label text): diabetes mellitus, diabetic ketoacidosis, myasthenia gravis, neuromuscular junction disease, hyperthyroidism, Graves disease, thyrotoxicosis, hypoglycaemia, atrioventricular block, pulmonary emphysema, bronchial disease and anaphylaxis. Several of these resemble beta-blocker cautions, so they may partly reflect the timolol combination product. They should be checked against the Product Information.
- Drug interactions: the interaction query returned four pharmacological target interactions, all with carbonic anhydrase isoforms (CA1, CA7, CA12, CA14). These describe drug targets, not drug-drug interactions with severity ratings.
Please refer to the TGA-approved Product Information (PI) for full warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The top-ranked prediction, hypotrichosis simplex of the scalp, rests on a model score alone, with no trials or publications. The hair and skin predictions have no plausible mechanism, and the cardiac and respiratory predictions have no efficacy evidence and little systemic exposure from eye drops.
To proceed, the following is needed:
- Mechanism of action data from DrugBank
- Product Information warnings and contraindications from the TGA, plus the approved indication text for the Australian entry
- Published or registered studies of dorzolamide in primary hereditary (including paediatric and congenital) glaucoma
- Review of how much the knowledge-graph contraindications reflect the timolol combination rather than dorzolamide alone
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.