Chlorthalidone
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Chlorthalidone: From Hypertension to Primary Hereditary Glaucoma
One-Sentence Summary
Chlorthalidone is a thiazide-like diuretic, originally used to treat hypertension and congestive heart failure. The TxGNN model predicts it may be effective for primary hereditary glaucoma, but there are currently 0 clinical trials and 0 publications supporting this prediction. The prediction is model-based only and should be treated as a hypothesis.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Hypertension, hypertensive disorder, congestive heart failure |
| Predicted New Indication | Primary hereditary glaucoma |
| TxGNN Prediction Score | 99.92% |
| Evidence Level | L5 |
| UK Market Status | Marketed |
| Number of Marketing Authorisations | 4 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available. Based on known information, chlorthalidone is a thiazide-like diuretic. Its efficacy in hypertension and heart failure is established, but a mechanistic link to primary hereditary glaucoma cannot be drawn from the data compiled for this report.
Thiazide-like diuretics are not an established glaucoma therapy. Chlorthalidone has weak carbonic anhydrase inhibitory activity, and carbonic anhydrase inhibitors lower intraocular pressure. This is a speculative link and is not supported by the data compiled here. The high TxGNN score therefore remains a model prediction only.
Other predicted indications (for context):
| Rank | Predicted Indication | Score | Evidence Level | Decision |
|---|---|---|---|---|
| 2 | Open-angle glaucoma | 99.90% | L5 | Hold |
| 3 | Malignant hypertensive renal disease | 99.89% | L5 | Hold |
| 4 | Malignant renovascular hypertension | 99.89% | L5 | Hold |
| 5 | Pulmonary hypertension owing to lung disease and/or hypoxia | 99.88% | L5 | Hold |
| 6 | Pulmonary hypertension with unclear multifactorial mechanism | 99.88% | L5 | Hold |
| 7 | Braddock syndrome | 99.85% | L5 | Hold |
| 8 | Chronic pulmonary heart disease | 99.82% | L4 | Research Question |
| 9 | Acute pulmonary heart disease | 99.32% | L5 | Hold |
| 10 | Congenital hypotrichosis milia | 99.19% | L5 | Hold |
Of these, chronic pulmonary heart disease has the most (though still weak) supporting evidence. Malignant hypertensive renal disease and malignant renovascular hypertension are biologically plausible because they relate to the approved hypertension indication, but neither has specific supporting data.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
No publications were found for primary hereditary glaucoma. The only literature found across the predicted indications is listed below for reference. It relates to other predicted indications, not to glaucoma.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 5597001 | 1967 | Clinical report (likely uncontrolled) | La Clinica terapeutica | Diuretic therapy with chlorthalidone in congestive heart failure caused by chronic cor pulmonale (relevant to chronic pulmonary heart disease) |
| 28711447 | 2017 | Review | JACC. Heart Failure | Update on the transition from hypertension to heart failure; only indirectly relevant |
| 14288313 | 1965 | Basic research | Journal of Cellular and Comparative Physiology | Ion transport in the Cecropia moth midgut; unrelated to human disease and gives no clinical support |
UK Market Information
Four marketing authorisations are recorded for products containing chlorthalidone. Authorisation numbers in MHRA format (PL numbers), dosage forms and approved indication texts were not available in the data compiled for this report. The identifiers below are those recorded.
| Identifier | Product Name | Type |
|---|---|---|
| 0202010F0BBAAAA | Hygroton Tab 50mg | Single-ingredient |
| 0202010F0AAAAAA | Chlortalidone Tab 50mg | Single-ingredient |
| 0202040V0BBAAAA | Kalspare Tab | Single-ingredient |
| 0202040V0AAAAAA | Triamterene/Chlortalidone Tab 50mg/50mg | Single-ingredient |
Please check the current MHRA records, the BNF and the relevant SmPCs for the licensed indications and formulations.
Safety Considerations
Contraindication-related conditions (from the knowledge graph, not label text): The knowledge graph links chlorthalidone to contraindication in the following conditions, which should be verified against the SmPC:
- Renal and hepatic: kidney disease, anuria, liver failure, pyoureter
- Metabolic: gout, hyperuricaemia, hypercalcaemia, nephrocalcinosis, potassium deficiency, phosphorus metabolism disease, type 2 diabetes mellitus and diabetes mellitus
- Cardiovascular: myocardial infarction, coronary thrombosis, sudden cardiac arrest
- Other: pancreatitis, peptic ulcer disease, systemic lupus erythematosus (including paediatric), asthma (intrinsic and allergic), psoriasis, parapsoriasis, epilepsy, anxiety disorder, neurotic disorder, dysthymic disorder, haemoglobinopathy
Drug Interactions: 210 interactions were recorded. Those most clinically important are:
- Major: cisapride, dolasetron
- Moderate (examples): acarbose, metformin, alogliptin, albiglutide (antidiabetic agents), hydrocortisone, dexamethasone, triamcinolone, beclomethasone (corticosteroids), amphotericin B, bupropion, morphine, omeprazole, rabeprazole, cholecalciferol
- Minor (examples): doxycycline, hyoscyamine, atropine
Please refer to the SmPC and BNF for full safety information. Report suspected adverse reactions via the Yellow Card Scheme.
Conclusion and Next Steps
Decision: Hold
Rationale: The TxGNN score for primary hereditary glaucoma is high, but no clinical trials or publications support it, and the mechanistic link is speculative. The evidence level is L5 (model prediction only).
To proceed, the following is needed:
- Mechanism of action data for chlorthalidone (currently unavailable)
- Preclinical or clinical evidence on intraocular pressure effects, including the carbonic anhydrase hypothesis
- A literature review focused on thiazide-like diuretics in glaucoma
- Label warnings and contraindications from the SmPC and BNF, and full MHRA licence details (PL numbers, dosage forms, indications)
- Consideration of an alternative priority: chronic pulmonary heart disease (L4, “Research Question”), where the evidence is limited to a 1967 clinical report and an indirectly relevant review
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.