Chlormadinone
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Chlormadinone: From Contraception (Oral Hormonal) to Antithrombin Deficiency Type 2
One-Sentence Summary
Chlormadinone is a synthetic progestogen (antigonadotropic and antiandrogenic) that is marketed in Singapore as part of an oral combined contraceptive product. The TxGNN model predicts it may be effective for antithrombin deficiency type 2, but no clinical trials and no supporting publications exist for this prediction. The prediction is a computational signal only, and the available evidence points more toward a thrombotic safety concern than a therapeutic benefit.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not stated in the registration data (the product is a combined oral contraceptive tablet) |
| Predicted New Indication | Antithrombin deficiency type 2 |
| TxGNN Prediction Score | 98.71% |
| Evidence Level | L5 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 1 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not currently available. Based on known information, chlormadinone is a progestogen with antigonadotropic and antiandrogenic activity. It is used in hormonal contraception, but no established mechanism links it to correcting antithrombin deficiency.
Antithrombin deficiency type 2 is a hereditary coagulation disorder that raises the risk of thrombosis. Hormonal agents are generally a thrombotic concern in this population rather than a treatment. The high score most likely reflects proximity to coagulation-related nodes in the knowledge graph, not a real pharmacological relationship.
The other top-ranked predictions show the same pattern:
| Rank | Predicted Indication | Score | Evidence Level | Assessment |
|---|---|---|---|---|
| 2 | Heparin cofactor 2 deficiency | 98.67% | L5 | No plausible pathway; likely graph proximity |
| 3 | Factor 5 excess with spontaneous thrombosis | 98.64% | L5 | Prothrombotic state; not expected to respond to a progestogen |
| 4 | Candidiasis | 98.62% | L5 | Only a 1967 general review; hormonal contraceptives are if anything linked to higher candidiasis risk |
| 5 | Plasma cell myeloma | 97.89% | L5 | No established link |
| 6 | Heart neoplasm | 97.77% | L5 | Only a general 1990 safety review |
| 7 | Rheumatoid arthritis | 97.72% | L5 | Only a 1971 biomarker observation in healthy women |
| 8 | Indolent plasma cell myeloma | 97.68% | L5 | Overlaps with the myeloma signal |
| 9 | Gout | 97.68% | L5 | No established link |
| 10 | Thrombophilia | 97.66% | L4 | Literature concerns safety of progestogen use, not treatment |
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
For the lead prediction (antithrombin deficiency type 2), currently no related literature is available.
The most relevant publications were found for the related prediction thrombophilia (rank 10). They concern the safety of progestogens in women at high thrombotic risk, not therapeutic benefit:
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 15541404 | 2004 | Cohort (retrospective) | Contraception | Compared women at high risk of venous thromboembolism using antigonadotropic-dose chlormadinone acetate (n=102) with matched women using no hormonal contraception; assesses the venous impact of progestogen-only contraception |
| 25961217 | 2010 | Review | Hormone Molecular Biology and Clinical Investigation | Antigonadotropic progestogens as contraceptive options for women who cannot use the combined pill |
| 15333036 | 2004 | Cohort (cross-sectional) | Journal of Thrombosis and Haemostasis | Assessed the effect of a chlormadinone acetate progestagen-only pill on activated protein C resistance |
| 1199513 | 1975 | Cohort | Zentralblatt fur Gynakologie | Fibrinolytic split products increased during use of several hormonal contraceptives, including a chlormadinone acetate combination |
Other single references found for lower-ranked predictions are general or biomarker papers that do not show efficacy: candidiasis (5337087, 1967 review), heart neoplasm (2170823, 1990 review of estrogen and progestogen risks) and rheumatoid arthritis (4994393, 1971 cohort of autoantibodies in healthy women using oral contraceptives).
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN14870P | BELARA film-coated tablet 0.03mg/2mg (Gedeon Richter Plc.) | Film-coated tablet (oral) | Not stated in the registration data |
Safety Considerations
Please refer to the package insert for safety information.
One point from the compiled literature deserves attention: progestogens may influence activated protein C resistance and coagulation markers, which is a thrombotic safety concern for patients with thrombophilia or inherited coagulation disorders. This needs careful evaluation before any use in such populations.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction rests only on a computational score, with no clinical trials and no publications for antithrombin deficiency type 2. There is no plausible mechanism, and hormonal agents are generally a thrombotic concern in this population. The same applies to the other top-ranked predictions, none of which is supported above L5 (thrombophilia reaches L4, but its literature addresses safety, not efficacy).
To proceed, the following is needed:
- The package insert warnings and contraindications for the registered product, which are not available and block safety screening
- Mechanism of action data for chlormadinone
- Evidence of a biological pathway linking chlormadinone to antithrombin or other coagulation-factor function, if one exists
- A thrombosis risk assessment specific to patients with hereditary coagulation disorders
- Review of the thrombophilia literature as a safety question (can chlormadinone be used as a contraceptive in this population) and not as a repurposing opportunity
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.