Nintedanib
| Evidence Level: L5 | Predicted Indications: 3 |
Table of Contents
Nintedanib: Dermatofibrosarcoma protuberans
One-Sentence Summary
Nintedanib was originally used for non-small cell lung carcinoma and fibrosing interstitial lung diseases such as idiopathic pulmonary fibrosis. The TxGNN model predicts it may be effective for Dermatofibrosarcoma Protuberans (DFSP), but at present only 1 review article supports this direction, and no clinical trials are registered.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Dermatofibrosarcoma protuberans |
| TxGNN Prediction Score | 0.9915 |
| Evidence Level | L5 |
| India Market Status | Listed in a compiled Indian medicine price dataset (at least 20) – CDSCO approval status is not included in this data |
| Number of Listed Products | at least 20 |
| 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, nintedanib is a small-molecule tyrosine kinase inhibitor that targets PDGFR-alpha/beta, FGFR1-3 and VEGFR1-3. Its efficacy in idiopathic pulmonary fibrosis and non-small cell lung carcinoma is established, and mechanistically it may be applicable to DFSP.
DFSP is driven by the COL1A1-PDGFB fusion, which causes constitutive activation of PDGFR-beta. Because nintedanib inhibits PDGFR-beta, there is a plausible biological link between the drug and this tumour. Its antifibrotic and antiproliferative effects on fibroblasts add a general supporting rationale.
This link is indirect, however. Imatinib is the established PDGFR-targeted agent for DFSP, and no nintedanib-specific clinical data are available. The prediction should therefore be treated as a research question rather than a treatment recommendation.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 29408302 | 2018 | Review | Pharmacological Research | Reviews small-molecule PDGFR inhibitors in neoplastic disorders; indirect support for targeting PDGFR in PDGF-driven tumours |
India Market Information
Twenty valid single-ingredient registrations are on record, all oral capsules. The licence records do not include approved indication text. Five main authorizations are listed below.
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 41026 | Cyendiv 100mg Soft Gelatin Capsule (Boehringer Ingelheim) | Bottle of 10 soft gelatin capsules | Not stated in the records |
| 150549 | Nintib 150 Soft Gelatin Capsule (Cipla Ltd) | Strip of 10 soft gelatin capsules | Not stated in the records |
| 151861 | Nindev 100mg Soft Gelatin Capsule (Zydus Cadila) | Strip of 10 soft gelatin capsules | Not stated in the records |
| 140002 | Mantedanib Capsule 150mg (Mankind Pharma Ltd) | Strip of 10 capsules | Not stated in the records |
| 150364 | Nintena 150mg Soft Gelatin Capsule (Sun Pharmaceutical Industries Ltd) | Strip of 10 soft gelatin capsules | Not stated in the records |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (tyrosine kinase inhibitor) |
| Myelosuppression Risk | Please refer to the package insert warnings and precautions |
| Emetogenicity Classification | Please refer to the package insert warnings and precautions |
| Monitoring Items | Please refer to the package insert warnings and precautions |
| Handling Protection | Please refer to the package insert warnings and precautions |
Safety Considerations
- Drug Interactions: 100 interactions were recorded. The first 20 returned include one Major interaction and 19 Moderate ones.
- Major: Dexamethasone.
- Moderate, bleeding-risk related: Acetylsalicylic acid, clopidogrel, apixaban, dalteparin, cilostazol, dipyridamole, alteplase, abciximab, bivalirudin, betrixaban, cangrelor, caplacizumab, defibrotide, desirudin, antithrombin III human. Anticoagulants, antiplatelets and thrombolytics warrant particular caution.
- Moderate, other: Clarithromycin, cobicistat, naltrexone, rolapitant.
Please refer to the package insert for other safety information, including warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction score is high (0.9915), and the PDGFR-beta mechanism is plausible for DFSP. However, the only supporting evidence is one indirect review, there are no clinical trials, and an established PDGFR-targeted therapy (imatinib) already exists. Safety review also cannot proceed until the package insert data are obtained.
To proceed, the following is needed:
- Package insert warnings and contraindications from the India Pharma source (a blocking data gap for safety screening)
- Detailed mechanism of action data from DrugBank
- Preclinical data (for example DFSP cell-line or xenograft studies) or case reports of nintedanib in DFSP
- A comparison against imatinib to define a possible role, such as in imatinib-resistant disease
- A bleeding-risk management plan for patients taking anticoagulants or antiplatelet agents
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.