Iloprost

Evidence Level: L5

Predicted Indications: 4

Iloprost

Pharmacist Assessment Report

Iloprost: Hypotrichosis simplex of the scalp

One-Sentence Summary

Iloprost is a stable prostacyclin analogue, originally used to treat pulmonary arterial hypertension (PAH). The TxGNN model’s top-ranked prediction is hypotrichosis simplex of the scalp, but this has no supporting studies. The best-supported prediction is PAH associated with congenital heart disease, backed by 19 publications (no registered clinical trials), most of them observational studies, reviews and case reports.

Quick Overview

Item	Content
Original Indication	Not recorded in the local data
Predicted New Indication	Hypotrichosis simplex of the scalp
TxGNN Prediction Score	0.9945
Evidence Level	L5 (hypotrichosis simplex of the scalp); L3 (PAH-CHD)
Australia Market Status	Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data
Number of PBS Items	1 (valid: 1)
Recommended Decision	Hold (top-ranked prediction); Proceed with Guardrails as a research question for PAH-CHD

Note on the top-ranked prediction: No clinical trials or literature support hypotrichosis simplex of the scalp. The direction of effect is also uncertain, because prostaglandin F2α analogues promote hair growth whereas PGD2 inhibits it. The report therefore focuses on the best-supported prediction, PAH-CHD, and summarises the other candidates below.

Why is This Prediction Reasonable?

Detailed mechanism of action data is not available in the data compiled for this report. Based on known pharmacology, iloprost is a stable prostacyclin (IP receptor) agonist. It causes pulmonary vasodilation, inhibits platelet aggregation and limits smooth muscle proliferation.

Summary of other predictions:

Predicted Indication	Score	Evidence Level	Assessment
Pulmonary arteriovenous malformation	0.9931	L5	Not mechanistically sensible, because vasodilation may worsen shunting and hypoxaemia

Clinical Trial Evidence

Currently no related clinical trials registered.

Literature Evidence

Selected publications for PAH associated with congenital heart disease:

PMID	Year	Type	Journal	Key Findings
31371115	2020	Placebo-controlled, double-blind randomised cross-over pilot study	Int J Cardiol	Nebulised iloprost in Eisenmenger syndrome, addressing limited safety and efficacy data in this group
29426959	2018	Cohort	Pediatr Cardiol	Safety and acute haemodynamic effects of inhaled iloprost in children with PAH-CHD
28608969	2017	Cohort	Clin Exp Pharmacol Physiol	Effect of iloprost on endothelial-dysfunction biomarkers in CHD-PAH
27492657	2017	Cohort	J Cardiol	Effect of long-term inhaled iloprost on right ventricular function in Eisenmenger syndrome
24729548	2015	Cohort	Pediatr Pulmonol	Long-term effects of inhaled iloprost in children with pulmonary hypertension
36010107	2022	Case series	Children (Basel)	Add-on sildenafil, bosentan and iloprost in 5 Eisenmenger syndrome patients followed 2010–2019
19436672	2009	Review	Vasc Health Risk Manag	Review of inhaled iloprost for paediatric pulmonary hypertension
22621693	2012	Review	Drugs	Treatment of PAH in connective tissue disease, including congenital heart disease as a related group

For PAH associated with connective tissue disease, the more relevant publications include 27651181 (2017, Respirology, cohort: long-term outcomes of domiciliary intravenous iloprost in idiopathic and CTD-associated PAH) and 25261325 (2015, Eur Respir J, preclinical: iloprost reversed established right ventricular fibrosis in rats).

Australia Market Information

ARTG Number	Product Name	Dosage Form	Approved Indication
ARTG 5751Q	Ventavis	Solution for inhalation 20 micrograms (as trometamol) in 2 mL	Not recorded in the data compiled for this report

Safety Considerations

Contraindication-related conditions (not label text): liver failure, chronic obstructive pulmonary disease (including severe early-onset), hypotensive disorders, pulmonary oedema and bronchial disease.
Drug Interactions: 100 interactions were identified. Those graded Moderate include epinephrine, acetylsalicylic acid (aspirin), SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin, ertugliflozin), inhaled human insulin, mannitol, ephedrine, fenfluramine, dexfenfluramine, glycerin, papaverine and sibutramine. Interactions with calcitriol, pantoprazole, morphine, metformin and omeprazole have an unknown severity grade.

Please refer to the TGA-approved Product Information (PI) for the full warnings and contraindications, as label-based safety data were not available.

Conclusion and Next Steps

Decision: Hold for the top-ranked prediction (hypotrichosis simplex of the scalp); Proceed with Guardrails as a research question for PAH associated with congenital heart disease

Rationale:

The top-ranked hair-related predictions have no trials or literature and an uncertain direction of effect, so they should not be progressed.
PAH-CHD and CTD-PAH are mechanistically coherent extensions of the approved indication, supported by observational data (L3). There is no phase 3 randomised evidence, so they remain research questions rather than ready-to-adopt indications.

To proceed, the following is needed:

Confirmation of the approved indication wording and PI-based warnings and contraindications from the TGA record (the ARTG indication text is blank in the compiled data)
Detailed mechanism of action data (for example from DrugBank)
Review of whether the current Australian PAH indication already covers PAH-CHD, to determine whether this is a true new indication
Controlled trial data for iloprost in PAH-CHD and Eisenmenger syndrome
A safety plan accounting for the contraindication-related conditions (hypotension, pulmonary oedema, COPD, liver failure) and for the interactions listed above
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.