Dacomitinib
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Dacomitinib: From Its Licensed Oncology Use to Rheumatoid Arthritis
One-Sentence Summary
Dacomitinib (brand name VIZIMPRO) is an oral pan-HER/EGFR tyrosine kinase inhibitor marketed in Singapore. The approved indication text is not available in the data compiled for this report. The TxGNN model predicts it may be effective for rheumatoid arthritis, but no clinical trials and no publications currently support this specific prediction. The evidence is model prediction only.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not available in the data compiled for this report (Singapore licence texts are empty) |
| Predicted New Indication | Rheumatoid arthritis |
| TxGNN Prediction Score | 97.79% |
| 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 compiled data. Based on known information, dacomitinib is an irreversible pan-HER/EGFR tyrosine kinase inhibitor, a class used in oncology. Mechanistically, EGFR signalling has been implicated in the proliferation of synovial fibroblasts, which is the only rationale linking it to rheumatoid arthritis.
This link is speculative. There is no clinical or published evidence for dacomitinib in rheumatoid arthritis. The known safety profile of the drug (rash, diarrhoea, interstitial lung disease) is also a concern for a chronic, non-oncology condition that requires long-term treatment.
Other predictions, for context. The model's other top predictions are also weakly supported:
- Pulmonary hypertension (score 96.51%, evidence level L4): The only candidate with published support. A 2019 preclinical study found that dacomitinib attenuated pulmonary vascular remodelling and pulmonary hypertension in rats. It is a research question rather than a clinical candidate, and pulmonary toxicity from EGFR inhibitors needs careful consideration.
- Multiple endocrine neoplasia (score 96.18%, L4): One terminated Phase 1 platform trial with 2 participants provides no usable signal.
- Homozygous familial hypercholesterolaemia, brachydactyly-syndactyly syndrome, nephrogenic syndrome of inappropriate antidiuresis, colobomatous microphthalmia-rhizomelic dysplasia syndrome, kyphoscoliotic heart disease, amyotrophic lateral sclerosis and leprosy: Prediction only, with no plausible mechanistic link identified.
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN15965P | VIZIMPRO FILM-COATED TABLET 45MG | Film-coated tablet | Not available |
| SIN15966P | VIZIMPRO FILM-COATED TABLET 15MG | Film-coated tablet | Not available |
| SIN15967P | VIZIMPRO FILM-COATED TABLET 30MG | Film-coated tablet | Not available |
All three licences are valid single-ingredient products from Pfizer Manufacturing Deutschland GmbH, given as oral tablets.
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (pan-HER/EGFR 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; skin, gastrointestinal and respiratory symptoms are relevant given the class |
| Handling Protection | Please refer to the package insert warnings and precautions |
Safety Considerations
- Drug Interactions: 94 interactions were identified. Those listed include:
- Major: the proton pump inhibitors rabeprazole, omeprazole, dexlansoprazole, esomeprazole, lansoprazole and pantoprazole, and also eliglustat.
- Moderate: the H2 blockers famotidine, ranitidine (including ranitidine bismuth citrate), cimetidine and nizatidine; also dexfenfluramine, fenfluramine, metoclopramide, promethazine, chlorpheniramine, codeine, dextromethorphan and diphenhydramine.
- Acid-suppressing drugs are the most prominent group and would need careful management.
- Class-related concerns: Rash, diarrhoea and interstitial lung disease are expected concerns for EGFR inhibitors. They are noted in the repurposing assessment and have not been confirmed against the package insert.
Please refer to the package insert for the full warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The rheumatoid arthritis prediction rests on a model score alone (L5), with no trials or literature. The drug's toxicity profile is difficult to justify for a chronic non-oncology indication.
To proceed, the following is needed:
- Singapore package insert (warnings, contraindications and approved indications), which is currently a blocking gap for safety screening
- Mechanism-of-action data from DrugBank
- Preclinical evidence of dacomitinib in rheumatoid arthritis models (for example, synovial fibroblast or arthritis animal models)
- A risk-benefit assessment of long-term EGFR inhibition in a non-oncology population
- Separately, pulmonary hypertension could be followed up as a research question, given the 2019 preclinical study (PMID 30753867), after its pulmonary safety is evaluated
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.