Phenylephrine
| Evidence Level: L3 | Predicted Indications: 3 |
Table of Contents
Phenylephrine: From Allergic Rhinitis and Nasal Congestion to Nasal Cavity Disease
One-Sentence Summary
Phenylephrine is an alpha-1 adrenergic agonist originally used for nasal and upper-airway conditions such as allergic rhinitis, vasomotor rhinitis, the common cold and pharyngitis, as well as for several eye and rectal conditions. The TxGNN model predicts it may be effective for nasal cavity disease, with no registered clinical trials and 5 publications (mostly reviews, indirect or safety-related reports) currently supporting this direction. This is largely an extension of existing indications, and the evidence is still at the research-question stage.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Allergic rhinitis, vasomotor rhinitis, pharyngitis, common cold, rhinitis, nasopharyngitis and others (the US license records contain no indication text, so this list comes from the knowledge graph) |
| Predicted New Indication | Nasal cavity disease |
| TxGNN Prediction Score | 99.97% |
| Evidence Level | L3 |
| US Market Status | Cancelled only (no currently valid licenses) |
| Number of NDAs | 12 (all cancelled) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on known pharmacology, phenylephrine is an alpha-1 adrenergic agonist. It constricts the blood vessels of the nasal mucosa, which reduces swelling, congestion and bleeding.
This is consistent with its existing uses in rhinitis and nasopharyngitis. “Nasal cavity disease” is a broad category that largely overlaps with these indications, so the prediction is more of an extension than a new therapeutic area.
The literature points to two kinds of use: topical phenylephrine-containing nasal sprays (such as Polydexa with phenylephrine) in inflammatory nasal disease, and surgical-field control during endoscopic sinus surgery. Only abstracts or titles were available, so study designs and results cannot be fully confirmed.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 40899890 | 2025 | Experimental and clinical evaluation (design unconfirmed) | Vestnik otorinolaringologii | Safety and efficacy of Polydexa spray with phenylephrine in acute rhinosinusitis; no toxic effects data previously reported |
| 37970776 | 2023 | Review | Vestnik otorinolaringologii | Pathogenesis-based treatment of inflammatory nose and sinus diseases; drugs should reduce hyperemia, swelling and mucus |
| 37184554 | 2023 | Review/Clinical (diagnostic) | Vestnik otorinolaringologii | Endoscopic assessment of the nasal mucosa after local anti-inflammatory and antibacterial therapy, including Polydexa with phenylephrine |
| 25133491 | 2014 | Randomized clinical trial (triple-blind) | PloS one | Topical tranexamic acid and bleeding during endoscopic sinus surgery; phenylephrine relevance is indirect |
| 7378007 | 1980 | Case report | Archives of ophthalmology | Toxicity after intranasal cocaine, with an additional reaction to intranasal phenylephrine; caution in hypertensive cardiovascular disease (safety-related, indirect) |
US Market Information
All 12 US authorizations are cancelled. The records contain no approved-indication text. Main entries:
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| NDA207926 | Phenylephrine Hydrochloride (Alcon Laboratories) | Solution/drops | Not recorded |
| ANDA218129 | Phenylephrine Hydrochloride (Dr. Reddy’s) | Solution/drops | Not recorded |
| part341 | CVS Health Four Actions Nasal Decongestant | Spray | Not recorded |
| M012 | Sinus Pressure and Congestion Relief PE (Rite Aid) | Tablet, film coated | Not recorded |
| ANDA211078 | Phenylephrine hydrochloride (Amneal) | Injection | Not recorded |
The remaining authorizations are injectable generics.
Safety Considerations
- Contraindication signals from the knowledge graph (not label text): hypertension and hypertensive disorders, liver failure and liver disease, kidney disease, epilepsy, chronic obstructive pulmonary disease, peptic ulcer and gastric ulcer, pancreatitis, hypothyroidism, adrenocortical insufficiency, porphyria, thrombocytopenia, inflammatory bowel disease, and psychotic disorders, among others.
- Drug Interactions (100 interactions found; the 20 listed are all Moderate): antidiabetic drugs (acarbose, glimepiride, glipizide, glyburide, chlorpropamide, acetohexamide, insulin human, insulin aspart), SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin, ertugliflozin), GLP-1 and DPP-4 agents (albiglutide, dulaglutide, exenatide, alogliptin), anticholinergics (atropine ophthalmic, clidinium, hyoscyamine), and diethylpropion.
- Literature signal: a case report describes toxicity with intranasal use alongside cocaine, and cautions against use in hypertensive cardiovascular disease or together with other sympathomimetics.
Please refer to the package insert for label warnings and contraindications, which were not available in the compiled data.
Conclusion and Next Steps
Decision: Hold
Rationale: The predicted indication largely overlaps with existing rhinitis and nasopharyngitis uses and is mechanistically plausible. However, there are no registered clinical trials, the literature is mostly reviews or indirect studies (L3), and all US licenses are cancelled. Label safety data are also missing.
To proceed, the following is needed:
- FDA package insert warnings and contraindications (a blocking gap for safety screening)
- Mechanism of action data from DrugBank
- Full texts of the key nasal-spray studies to confirm design, comparators and outcomes
- A clearly defined nasal cavity disease subtype and a route and formulation plan (the US topical nasal products are currently cancelled)
- A cardiovascular and drug interaction risk assessment, particularly for hypertensive patients and those taking antidiabetic drugs
Additional Predicted Indications (for Reference)
- Acute laryngopharyngitis (score 99.97%, L5, Hold): no clinical trials or literature. The prediction likely reflects similarity to existing pharyngitis indications.
- Trigeminal autonomic cephalalgia (score 99.30%, L4, Hold): 13 publications, almost all observational pupillometry studies in cluster headache and related conditions. They use phenylephrine as a diagnostic probe of sympathetic function, not as a treatment, so they provide no therapeutic evidence. Systemic vasoconstriction and hypertension risks are a concern.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.