Alprostadil
| Evidence Level: L3 | Predicted Indications: 10 |
Table of Contents
- Alprostadil
- Alprostadil: From Erectile Dysfunction and Ductal-Dependent Congenital Heart Disease to Aortic Malformation
Alprostadil: From Erectile Dysfunction and Ductal-Dependent Congenital Heart Disease to Aortic Malformation
One-Sentence Summary
Alprostadil (prostaglandin E1) was originally used for erectile dysfunction and for keeping the ductus arteriosus open in newborns with certain congenital heart defects. The TxGNN model predicts it may be effective for aortic malformation, but this is largely an extension of its existing use rather than a true new indication. Currently 0 clinical trials and 8 publications (mostly case reports, cohort studies and indirect studies) support this direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Erectile dysfunction, psychologic dyspareunia, premature ejaculation, tricuspid atresia, coarctation of the aorta, tetralogy of Fallot, and double outlet right ventricle with pulmonary stenosis (from the knowledge-graph indication list; the Singapore licence records contain no indication text) |
| Predicted New Indication | Aortic malformation |
| TxGNN Prediction Score | 99.98% |
| Evidence Level | L3 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 2 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on known pharmacology, alprostadil is a prostaglandin E1 (PGE1) that relaxes smooth muscle and dilates blood vessels. In newborns, it keeps the ductus arteriosus open, which maintains blood flow in heart defects that depend on the duct for survival.
Coarctation of the aorta is already among the drug's original indications. Aortic malformation, which covers related lesions such as interrupted aortic arch, relies on the same logic: keeping the duct open allows blood to reach the body until surgery can be performed. The prediction is therefore mechanistically sound, though it is better described as an extension of established use than as a new therapeutic direction.
Secondary effects, such as reducing inflammation and lung injury after cardiopulmonary bypass or protecting tissue from ischaemia-reperfusion injury, are plausible but come from indirect or preclinical studies.
Other predicted indications (rank 2 to 8) are tricuspid and double outlet right ventricle variants. They score very high (above 99.9%), but this reflects closeness to existing indications in the knowledge graph; no direct evidence supports them. Endemic goiter (rank 10) has no plausible mechanistic link and is likely a knowledge-graph artifact.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 6763200 | 1982 | Cohort | Pharmacotherapy | Evaluation of alprostadil in infants with congenital heart disease; infusion dilates the ductus and increases pulmonary blood flow in lesions with right ventricular outflow obstruction |
| 19080093 | 2008 | Clinical study (indirect) | Zhonghua Yi Xue Za Zhi | Alprostadil and ulinastatin for inflammatory response and lung injury after cardiopulmonary bypass in children with congenital heart disease |
| 41167776 | 2025 | Cohort | Zhonghua Fu Chan Ke Za Zhi | Delivery mode and timing in 123 fetuses with complex congenital heart disease |
| 42469655 | 2026 | Cohort | BMC Pregnancy Childbirth | Integrated pregnancy and perinatal management of complex fetal congenital heart disease |
| 15362549 | 2004 | Review | Kyobu Geka | Transposition of the great arteries; alprostadil keeps the ductus open to protect left ventricular function before arterial switch surgery |
| 19068708 | 2008 | Case report | Kyobu Geka | Neonate with interrupted aortic arch type B managed with alprostadil, single-stage repair and haemodiafiltration; survived |
| 30184041 | 2018 | Case report | Braz J Cardiovasc Surg | Complex aortopulmonary window; milrinone and alprostadil used before surgery to counteract high lung pressure |
| 20029353 | 2009 | Preclinical (rat) | Minerva Chir | Alprostadil attenuated ischaemia-reperfusion injury in rat skeletal muscle |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN08097P | CAVERJECT POWDER FOR INJECTION 20 mcg/ml | Injection, powder, for solution | Not stated in the licence record |
| SIN02280P | PROSTIN VR PAEDIATRIC INJECTION 0.5 mg/ml | Injection | Not stated in the licence record |
Safety Considerations
Contraindications (from the knowledge graph, not label text): The knowledge graph links alprostadil to contraindications in the following groups. These should be verified against the package insert.
- Respiratory: newborn respiratory distress syndrome, acute respiratory distress syndrome, lung disease
- Blood and bone marrow: blood coagulation disease, sickle cell anaemia and related haemoglobinopathies, polycythaemia, thrombocytosis, leukaemia (including lymphoid and myeloid), plasma cell myeloma
- Penile and urinary conditions: priapism, Peyronie disease, penile fibromatosis, urethral stricture, urethritis, balanitis and balanoposthitis
- Other: hypotensive disorder, pyloric stenosis
Reported adverse effects in the literature: Prolonged PGE1 infusion in neonates has been linked to hypertrophic pyloric stenosis and gastric outlet obstruction, pseudo-Bartter syndrome (electrolyte disturbance), and, among more common effects, fever, apnoea, flushing and diarrhoea. Monitoring is needed during prolonged infusion.
Drug Interactions: 59 interactions were recorded. Moderate-level interactions were found with the SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin, ertugliflozin), lorcaserin and sapropterin. Others, such as morphine, metformin, omeprazole, pantoprazole, vancomycin, atropine and prednisone, are listed with unclassified severity.
For warnings and contraindications from the approved label, please refer to the package insert.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: The use of alprostadil to keep the ductus arteriosus open in aortic lesions is well established and already covers coarctation of the aorta, so the predicted indication is mainly an extension of existing use. Evidence is limited to cohort studies, case reports and indirect studies, with no registered trials. The other predicted indications (rank 2 to 10) have no direct evidence and should stay on Hold, apart from heart septal defect, which is a research question supported only by case reports.
To proceed, the following is needed:
- Package insert warnings and contraindications for the Singapore products (HSA)
- Detailed mechanism of action data
- Confirmation of the approved indications on the two Singapore licences; CAVERJECT is likely for erectile dysfunction and PROSTIN VR PAEDIATRIC for ductal patency, but the records contain no indication text
- A neonatal monitoring plan for prolonged infusion (apnoea, electrolytes, gastric outlet obstruction)
- Review of the knowledge-graph contraindications against the label
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.