Fosaprepitant
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
- Fosaprepitant
- Fosaprepitant: From Chemotherapy-Associated Nausea and Vomiting to Nephrogenic Syndrome of Inappropriate Antidiuresis
Fosaprepitant: From Chemotherapy-Associated Nausea and Vomiting to Nephrogenic Syndrome of Inappropriate Antidiuresis
One-Sentence Summary
Fosaprepitant is an intravenous prodrug of aprepitant, an NK1 receptor antagonist. Its approved indication text is not available in the data compiled for this report, but the drug class is used for nausea and vomiting prevention. The TxGNN model predicts it may be effective for nephrogenic syndrome of inappropriate antidiuresis, but no clinical trials and no publications currently support this prediction. This is a computational prediction only, and it should be treated with caution.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not available (the approved indication text is blank in all Singapore licences) |
| Predicted New Indication | Nephrogenic syndrome of inappropriate antidiuresis |
| TxGNN Prediction Score | 99.92% |
| 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. Fosaprepitant is known to be a prodrug of aprepitant, which blocks the NK1 (substance P) receptor. Its use in nausea and vomiting is well established, but that information is not in the compiled data, so the original indication is not confirmed here.
The link to the predicted indication is weak. Nephrogenic syndrome of inappropriate antidiuresis is caused by gain-of-function mutations in the vasopressin V2 receptor. NK1 antagonism is not known to act on this receptor or pathway. The high score of 99.92% reflects a computational, network-based prediction. It is not backed by any mechanism, trial or publication in the supplied data.
Other top predictions were also reviewed (pneumocystosis, leprosy, cryptococcal meningitis, multiple endocrine neoplasia, intracranial abscess, malaria, echinococcosis, hyperargininemia). None has any clinical or literature support, and none has an established mechanistic rationale. The only prediction with any supporting evidence is retinitis (rank 7, score 99.68%), which has one preclinical study (see below).
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
No literature is available for the top predicted indication. For reference, the only publication found among the top 10 predictions concerns retinitis (rank 7):
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 32058829 | 2021 | Preclinical (mouse model) | Ocular Immunology and Inflammation | Fosaprepitant, a substance P receptor antagonist, blocked UVR-B-induced NK1R expression in ocular tissues, in both the exposed and the unexposed partner eye. |
This is indirect, non-clinical evidence from a UV-induced ocular damage model, not from retinitis patients.
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN14150P | Emend® I.V. Powder for Solution for Infusion 150mg | Lyophilised powder for injection | Not stated |
| SIN16996P | APRITANT IV powder for solution for injection 150mg/vial | Lyophilised powder for injection | Not stated |
| SIN16419P | FOSAPREPITANT-AFT POWDER FOR INJECTION 150MG/VIAL | Lyophilised powder for injection | Not stated |
Safety Considerations
- Disease-related contraindication signal (knowledge graph, not label text): liver failure.
- Drug Interactions: 100 interactions were identified in total. The main ones in the data compiled for this report are:
- Major: eliglustat, naloxegol
- Moderate (examples): corticosteroids (dexamethasone, hydrocortisone, betamethasone, budesonide, triamcinolone), clarithromycin, cimetidine, proton pump inhibitors (rabeprazole, lansoprazole), miconazole, dronabinol, and antidiabetic agents (pioglitazone, glimepiride, saxagliptin, nateglinide)
Please refer to the package insert for the full 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 the proposed mechanism is not plausible given that the disorder arises from V2 receptor gain-of-function. The evidence level is L5.
To proceed, the following is needed:
- Package insert warnings and contraindications from HSA (a blocking gap for safety screening)
- Approved indication text and mechanism of action data for fosaprepitant
- Any mechanistic or preclinical evidence linking NK1 antagonism to the predicted indication
- Consideration of retinitis (L4, preclinical evidence only) as a possible research question, which would need further mechanistic and clinical investigation
- Review of the liver failure contraindication signal and the major drug interactions before any new use is considered
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.