Tromethamine
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Tromethamine: From Allergic Conjunctivitis to Allergic Urticaria
One-Sentence Summary
Tromethamine was originally linked to allergic eye conditions (atopic, papillary and vernal conjunctivitis) in the knowledge graph used by the model, and in the US it is also marketed as an injectable alkalinizing agent and as the salt form of fosfomycin. The TxGNN model predicts it may be effective for Allergic Urticaria, but there are 0 clinical trials and only 1 publication (a case report of an adverse reaction to a different drug), so the evidence is essentially model prediction only.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Atopic conjunctivitis, papillary conjunctivitis, vernal conjunctivitis (from the knowledge graph; no approved-indication text is available in the US license records) |
| Predicted New Indication | Allergic urticaria |
| TxGNN Prediction Score | 99.91% |
| Evidence Level | L5 |
| US Market Status | Cancelled only (no currently valid licenses) |
| Number of NDAs | 9 (all cancelled) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available. Tromethamine is known as a buffer and alkalinizing agent, and it is also used as a salt-forming partner in other drugs such as ketorolac tromethamine and fosfomycin tromethamine.
The high prediction score is most likely driven by the drug’s association with allergic conjunctivitis in the knowledge graph. Allergic conjunctivitis and allergic urticaria are both allergic or atopic conditions, so the model links them. There is no direct evidence that tromethamine itself acts on the allergic pathway.
The only publication retrieved describes a biphasic anaphylactic reaction to ketorolac tromethamine. This is an adverse-event report about the NSAID, with tromethamine only as the salt form. It is not evidence of benefit, and the high score should not be read as a signal of efficacy.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 16831313 | 2006 | Case report | Int J Immunopathol Pharmacol | Biphasic anaphylactic reaction to ketorolac tromethamine, an adverse event caused by the NSAID, not a treatment benefit |
US Market Information
All nine US licenses are cancelled. No approved-indication text is available in the data compiled for this report.
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| NDA013025 | THAM | Injection, solution | Not available |
| ANDA211558 | Tromethamine | Injection, solution | Not available |
| ANDA213116 | Tromethamine | Injection, solution | Not available |
| ANDA217608 | Fosfomycin tromethamine | Granule, for solution | Not available |
| ANDA214554 | Fosfomycin tromethamine | Granule, for solution | Not available |
Four further licenses (all fosfomycin tromethamine, also cancelled) are not shown.
Safety Considerations
- Disease-level contraindication signals (knowledge graph, not label text): The graph lists many conditions, including hypertension, kidney disease and impaired renal function, anuria, liver disease, diabetes and diabetic ketoacidosis, respiratory failure, asthma, peptic and gastric ulcer, inflammatory bowel disease, rheumatoid arthritis, bleeding disorders (hemophilia, blood coagulation disease), stroke and cerebrovascular disorders, myocardial infarction, and anemia or hemoglobinopathy. These likely partly reflect the ketorolac tromethamine salt form (NSAID) and should be verified against actual labels.
- Drug Interactions: 30 interactions were identified, and 20 are listed in the data compiled for this report. Moderate-level interactions include doxycycline, tetracycline, minocycline, acetylsalicylic acid, choline salicylate, ephedrine, pseudoephedrine, amphetamine, dextroamphetamine, benzphetamine and methenamine. Minor-level interactions include sulfonylureas (chlorpropamide, acetohexamide, glipizide, glyburide, tolazamide, tolbutamide), memantine and methotrexate.
Package insert warnings and contraindications were not available, so please refer to the package insert for full safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction rests on model output alone (L5). There are no clinical trials, and the single publication is an adverse-event report about a different drug, so it does not support efficacy. All US licenses are cancelled, and the mechanism and package insert safety data are missing.
To proceed, the following is needed:
- Mechanism of action data for tromethamine, and a plausible link to allergic urticaria
- FDA package insert warnings and contraindications (a blocking gap for safety screening)
- Evidence that tromethamine itself, not a partner drug, has activity in allergic or urticarial models
- Clarification of which formulation and route would be relevant to the new indication
Other predictions worth noting: Among the other predictions, only otitis externa has indirect support, at L4 (research question). It is based on in vitro and canine studies of Tris-EDTA, in which tromethamine acts as a buffer or adjuvant alongside EDTA to permeabilize Gram-negative bacteria and potentiate antibiotics. This evidence is veterinary, and human validation would be required.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.