Cholecalciferol
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
- Cholecalciferol
- Cholecalciferol: From Osteoporosis and Vitamin D Deficiency to Familial Isolated Hypoparathyroidism
Cholecalciferol: From Osteoporosis and Vitamin D Deficiency to Familial Isolated Hypoparathyroidism
One-Sentence Summary
Cholecalciferol (vitamin D3) is a long-established treatment for vitamin D deficiency, rickets, osteomalacia, osteoporosis and hypoparathyroidism. The TxGNN model predicts it may be effective for familial isolated hypoparathyroidism due to impaired PTH secretion. There are currently 0 clinical trials and 0 publications supporting this specific prediction, and hypoparathyroidism is already an existing indication, so this is not a true repurposing candidate.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Osteoporosis, vitamin D deficiency, rickets, osteomalacia, hypoparathyroidism, and related calcium and phosphate disorders (from the knowledge graph; the Singapore licence records carry no indication text) |
| Predicted New Indication | Familial isolated hypoparathyroidism due to impaired PTH secretion |
| TxGNN Prediction Score | 99.79% |
| Evidence Level | L5 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 3 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Cholecalciferol is a vitamin D pro-hormone. It is converted in the liver and kidney to the active form, calcitriol, which raises calcium and phosphate absorption and supports bone mineralisation. Its efficacy in correcting vitamin D deficiency and rickets is well established.
Hypoparathyroidism is already listed among cholecalciferol's original indications. In this condition, low parathyroid hormone (PTH) leads to low calcium, and vitamin D metabolites are used to help restore calcium balance. The familial isolated form is a genetic subtype of the same problem, so the model's high score likely reflects this overlap rather than a new therapeutic discovery. Native cholecalciferol also depends on PTH-driven kidney activation, so active analogues such as calcitriol or alfacalcidol are usually preferred when PTH is deficient. This point has not been verified in the data compiled here.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
Currently no related literature available.
Singapore Market Information
| Authorization Number | Product Name | Dosage Form |
|---|---|---|
| SIN15254P | D-CURE ORAL SOLUTION 25000IU | Solution |
| SIN17171P | GP CHOLECALCIFEROL SOFTGEL CAPSULE 25,000 IU | Capsule, liquid filled |
| SIN11975P | CERNEVIT FOR INJECTION | Injection, powder, for solution |
All three licences are valid single-ingredient registrations with no cancellations. Approved indication text is not available in the registration records.
Safety Considerations
- Contraindications (knowledge-graph associations, not label text): Conditions linked to cholecalciferol include:
- hypercalcaemia, nephrocalcinosis and phosphorus metabolism disorders;
- hyperparathyroidism and osteitis fibrosa;
- kidney, liver and gallbladder disease;
- sarcoidosis;
- hypertension and atrial fibrillation;
- diabetes and diabetic ketoacidosis;
- several iron-overload and other metabolic disorders (e.g. hemochromatosis, Wilson disease);
- hyperlipidaemia;
- breast and prostate cancers.
- Drug Interactions: 56 interactions were identified. Among those shown:
- Major: other vitamin D agents (calcifediol, calcitriol, dihydrotachysterol, doxercalciferol), with a risk of additive hypercalcaemia.
- Moderate: thiazide diuretics, barbiturates, carbamazepine, bile-acid sequestrants (cholestyramine, colestipol, colesevelam), and digoxin and digitoxin.
- Minor: cimetidine.
Please refer to the package insert for key warnings and formal contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction rests on the model score alone. No trials or literature were found for this form of hypoparathyroidism. The indication already overlaps with cholecalciferol's existing labelled use, so it adds no real new indication.
Two other predicted indications in the same analysis have much stronger support:
- Renal osteodystrophy has a Phase 3 trial (NCT00752401, status unknown) and was graded L1 with "Proceed with Guardrails".
- Impaired renal function (chronic kidney disease) has 15 trials, including a completed Phase 3 trial (NCT00968877). It was also graded L1 with "Proceed with Guardrails".
In both, benefit for biochemical correction (25(OH)D, PTH) is plausible, but clinical outcome benefit is not shown in the data compiled here. These two are better candidates for further evaluation.
To proceed, the following is needed:
- Mechanism of action data and the Singapore package insert warnings and contraindications.
- Evidence specific to familial isolated hypoparathyroidism, or confirmation that it falls under the existing hypoparathyroidism indication.
- For the kidney-related candidates, verified trial outcomes and a monitoring plan for calcium, phosphate and PTH, with hypercalcaemia avoidance.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.