Terlipressin
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Terlipressin: From Its Registered Use to Open-Angle Glaucoma
One-Sentence Summary
Terlipressin is a vasopressin analogue (a prodrug of lysine-vasopressin) that is marketed in Singapore as an injectable. The registration records compiled for this report do not state its approved indication. The TxGNN model predicts it may be effective for open-angle glaucoma, but this rests on the model score alone, with 0 clinical trials and 0 relevant publications. Among the other top-10 predictions, only pulmonary hypertension has any supporting literature (small hemodynamic studies and case reports).
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not stated in the Singapore registration records compiled |
| Predicted New Indication | Open-angle glaucoma |
| TxGNN Prediction Score | 99.78% |
| Evidence Level | L5 (model prediction only) |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 2 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Terlipressin is a vasopressin V1 receptor agonist and a prodrug of lysine-vasopressin. Its main pharmacological effect is vasoconstriction, notably in the splanchnic circulation, which lowers portal pressure.
The data compiled for this report do not support a plausible route from this mechanism to lower intraocular pressure. The high TxGNN score (0.998) is a statistical prediction from the knowledge graph. No trials, mechanistic studies, or relevant papers back it. Systemic vasoconstriction could, in principle, be a concern for ocular perfusion, so the prediction needs careful scrutiny.
Several other top predictions are also unsupported: primary hereditary glaucoma, "glaucoma 1, open angle" (a near-duplicate of the first prediction), and the generic "glaucoma". The same applies to esotropia, hyperthyroidism, kyphoscoliotic heart disease, headache disorder, and trigeminal autonomic cephalalgia. Headache is a recognised adverse effect of terlipressin, which argues for caution in headache-related indications.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
Currently no related literature available for open-angle glaucoma.
The only paper retrieved for the generic "glaucoma" prediction (PMID 31841026, 2020) is a randomized trial on dobutamine reversing terlipressin's cardio-suppressive effects in cirrhosis. It is not about glaucoma and was treated as a false-positive match.
Other Prediction with Supporting Literature: Pulmonary Hypertension
Pulmonary hypertension (TxGNN score 99.56%) is the only prediction in the top 10 with relevant literature. It reaches L3 evidence, with a "Research Question" recommendation. No registered clinical trials were found.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 22893473 | 2012 | Small cohort | Hepatobiliary Pancreat Dis Int | In 7 cirrhotic patients with pulmonary hypertension, the first terlipressin dose (2 mg) decreased pulmonary vascular resistance |
| 21733953 | 2012 | Small cohort | Angiology | Echo study comparing terlipressin's effects on pulmonary and systemic hemodynamics in cirrhosis with and without pulmonary hypertension |
| 18280605 | 2008 | Case report | J Hepatol | Significant reduction in pulmonary arterial pressure after 1 week of terlipressin in portopulmonary hypertension |
| 15259082 | 2004 | Echo study | World J Gastroenterol | Assessed terlipressin's effect on systolic pulmonary artery pressure in cirrhosis |
| 32999121 | 2020 | Case report | Indian Pediatr | Rescue treatment of persistent pulmonary hypertension and refractory shock in a preterm infant |
Caveats:
- V1 agonism can also raise pulmonary vascular resistance in other settings, so effects are context-dependent.
- Much of the retrieved literature concerns portal hypertension, a different condition, and should not be counted as direct evidence.
- Some study designs could not be confirmed because titles and abstracts were truncated.
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN17190P | TERLIPRESSIN-AFT Solution for Injection 0.85 mg/8.5 mL | Injection, solution | Not listed in the record |
| SIN14244P | GLYPRESSIN Solution for Injection 1 mg/8.5 mL | Injection, solution | Not listed in the record |
Both are valid single-ingredient licences, and neither is cancelled. They are injectable products only; no ophthalmic (eye-drop) formulation is registered, which is a further barrier for a glaucoma indication.
Safety Considerations
- Drug Interactions: No interaction records were found in the data compiled.
- Theoretical concern: Systemic vasoconstriction could, in principle, compromise ocular perfusion.
- Adverse effect: Headache is a recognised adverse effect of terlipressin.
Please refer to the package insert for full warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The glaucoma predictions rest solely on a model score. There are no trials or relevant publications, no plausible mechanism, and no ophthalmic formulation, and there is a theoretical ocular perfusion concern. Pulmonary hypertension is the only prediction with any supporting data, and even that is small, mostly observational, and context-dependent.
To proceed, the following is needed:
- Package insert warnings and contraindications, and the approved indications for the two Singapore licences
- Detailed mechanism-of-action data (for example, from DrugBank)
- A mechanistic or preclinical rationale linking V1 agonism to intraocular pressure, if glaucoma is to be pursued
- For pulmonary hypertension: a systematic review and well-designed prospective studies that separate pulmonary from portal hypertension populations, plus a safety assessment of pulmonary vascular resistance effects
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.