Pasireotide
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
- Pasireotide
- Pasireotide: From Cushing Syndrome to Nephrogenic Syndrome of Inappropriate Antidiuresis
Pasireotide: From Cushing Syndrome to Nephrogenic Syndrome of Inappropriate Antidiuresis
One-Sentence Summary
Pasireotide is a somatostatin analogue originally used to treat Cushing syndrome (adrenal gland hyperfunction). The TxGNN model predicts it may be effective for nephrogenic syndrome of inappropriate antidiuresis (NSIAD), but no clinical trials and no publications currently support this prediction. It is a computational prediction only.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Adrenal gland hyperfunction; Cushing syndrome (the Singapore licence records contain no approved indication text) |
| Predicted New Indication | Nephrogenic syndrome of inappropriate antidiuresis |
| TxGNN Prediction Score | 96.12% |
| Evidence Level | L5 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 3 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the data compiled for this report. Based on known pharmacology, pasireotide is a multi-receptor somatostatin analogue (acting on SSTR1, 2, 3 and 5). It suppresses ACTH, growth hormone and IGF-1, which is why it works in Cushing syndrome.
NSIAD is caused by gain-of-function variants in the vasopressin V2 receptor (AVPR2), which leads to inappropriate water retention. A link between somatostatin receptor agonism and water balance could only be indirect, for example through modulation of vasopressin or cAMP signalling. No direct mechanism has been established.
The high score (96.12%) should therefore be treated as a hypothesis from network proximity in the knowledge graph, not as biological confirmation. The other nine predictions in the ranking (for example Ambras-type hypertrichosis, hyperargininemia and tinea nigra) also have no supporting evidence and no credible mechanism.
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 | Approved Indication |
|---|---|---|---|
| SIN15168P | SIGNIFOR LAR 20 mg powder and solvent for suspension for injection | Injection, powder, for suspension | Not stated in licence records |
| SIN15169P | SIGNIFOR LAR 40 mg powder and solvent for suspension for injection | Injection, powder, for suspension | Not stated in licence records |
| SIN15170P | SIGNIFOR LAR 60 mg powder and solvent for suspension for injection | Injection, powder, for suspension | Not stated in licence records |
All three licences are valid single-ingredient products, and none has been cancelled. Pasireotide is available only as an injectable in Singapore.
Safety Considerations
- Drug Interactions: 100 interactions were identified. Those listed below are the Major ones among the 20 interactions reviewed for this report:
- Clarithromycin
- Dolasetron
- Palonosetron
Most of the other interactions reviewed are Moderate. They include antidiabetic agents (acarbose, metformin, pioglitazone, alogliptin, saxagliptin, linagliptin, canagliflozin, dapagliflozin, empagliflozin, chlorpropamide, albiglutide, dulaglutide), laxatives (bisacodyl, picosulfuric acid, polyethylene glycol), loperamide and famotidine. Co-administration with antidiabetic drugs needs attention because pasireotide can affect glucose control.
Please refer to the package insert for warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction is supported only by a model score. There are no clinical trials or publications, and no plausible mechanism links somatostatin receptor agonism to NSIAD, which is driven by AVPR2 gain-of-function. Because the evidence level is L5, the project should not advance.
To proceed, the following is needed:
- Detailed mechanism of action data for pasireotide, and an analysis of any link to vasopressin or cAMP signalling
- Preclinical or case-level evidence for NSIAD (for example, in vitro AVPR2 gain-of-function models)
- Approved indication text, warnings and contraindications from the HSA package inserts
- Review of route and formulation compatibility (only a long-acting injectable is registered in Singapore)
- A safety assessment covering hyperglycaemia, hepatic effects and the major drug interactions listed above
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.