Selpercatinib
| Evidence Level: L5 | Predicted Indications: 3 |
Table of Contents
- Selpercatinib
- Pharmacist Assessment Report
- Selpercatinib: From an Unspecified Original Indication to Pulmonary Hypertension
- One-Sentence Summary
- Quick Overview
- Why is This Prediction Reasonable?
- Clinical Trial Evidence
- Literature Evidence
- Australia Market Information
- Cytotoxicity
- Safety Considerations
- Conclusion and Next Steps
- Disclaimer
Selpercatinib: From an Unspecified Original Indication to Pulmonary Hypertension
One-Sentence Summary
Selpercatinib is a selective RET kinase inhibitor marketed in Australia as Retevmo. The data compiled for this report do not state its approved indication. The TxGNN model predicts it may be effective for pulmonary hypertension, but there are no registered clinical trials and no publications that directly address this prediction. The prediction is model-based only and the direction of effect is uncertain.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not available in the data compiled for this report (the ARTG entry has no indication text) |
| Predicted New Indication | Pulmonary hypertension |
| TxGNN Prediction Score | 0.9918 |
| Evidence Level | L5 |
| Australia Market Status | Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data |
| Number of PBS Items | 1 (valid: 1) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the data compiled for this report. Selpercatinib is known to be a selective RET kinase inhibitor, and the literature retrieved relates to RET-driven cancers (RET fusion-positive non-small-cell lung cancer and medullary thyroid carcinoma). The original indication could not be confirmed from the Australian licence record.
No plausible RET-driven mechanism in pulmonary hypertension is established in the supplied data. The high TxGNN score reflects proximity in a knowledge network rather than demonstrated biology. Some multikinase inhibitors have been linked to pulmonary hypertension as an adverse effect, so the direction of effect is uncertain and could be harmful.
Other top-ranked predictions are also unsupported. These include migraine disorder and its subtypes, idiopathic pulmonary arterial hypertension, heritable pulmonary hypertension, and several rare skeletal or dermatological entries. Several look like TxGNN model (deep learning) artefacts. Kinase inhibitors such as imatinib have been explored in pulmonary arterial hypertension, but selective RET inhibitors have not.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
The publications retrieved do not test selpercatinib in pulmonary hypertension. They are listed for context only.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 39372206 | 2024 | Real-world pharmacovigilance study | Front Pharmacol | Compares adverse event profiles of pralsetinib and selpercatinib using FDA adverse event reports |
| 34178121 | 2021 | Retrospective cohort | Ther Adv Med Oncol | Real-world use of selpercatinib in RET fusion-positive NSCLC through an access program (SIREN) |
| 41918669 | 2026 | Case report | Cureus | Long-term management of metastatic medullary thyroid carcinoma with RET M918T mutation in MEN 2B, including targeted therapy |
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ARTG 14693H | Retevmo | Capsule 40 mg | Not stated in the data compiled |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (selective RET kinase inhibitor) |
| Myelosuppression Risk | Please refer to the Product Information (PI) warnings and precautions |
| Emetogenicity Classification | Please refer to the Product Information (PI) warnings and precautions |
| Monitoring Items | Please refer to the Product Information (PI) warnings and precautions |
| Handling Protection | Please refer to the Product Information (PI) warnings and precautions |
Safety Considerations
- Drug Interactions: The interaction screen returned 100 interacting drugs, including many rated Major. The main Major interactions listed include:
- Acid-suppressing agents: famotidine, ranitidine, cimetidine, omeprazole, rabeprazole, dexlansoprazole
- Magnesium oxide
- Aprepitant
- Clarithromycin
- Dexamethasone
Moderate interactions include hydrocortisone, triamcinolone, betamethasone, budesonide, pioglitazone, loperamide, bisacodyl, saxagliptin and polyethylene glycol with electrolytes.
- Pulmonary vascular concern: Safety signals for kinase inhibitors in the pulmonary vasculature warrant caution if pulmonary hypertension is pursued.
For warnings and contraindications, please refer to the TGA-approved Product Information (PI).
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction is supported only by a network-based model score. There are no trials, no relevant literature, and no established mechanism, and a harmful effect on the pulmonary vasculature cannot be excluded.
To proceed, the following is needed:
- Confirmed approved indication and Product Information from the TGA record
- Mechanism of action data and a plausible biological link between RET inhibition and pulmonary hypertension
- Preclinical evidence in pulmonary hypertension models, including assessment of pulmonary safety signals
- Review of pharmacovigilance data for pulmonary hypertension events with selpercatinib
- Product Information warnings, contraindications and interaction management plan before any clinical evaluation
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.