Misoprostol
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
Misoprostol: From Gastric Ulcer Prevention to Amenorrhea
One-Sentence Summary
Misoprostol is a prostaglandin E1 analogue, marketed in Singapore as Cytotec tablets, and it is best known for protecting the stomach lining. The TxGNN model predicts it may be effective for amenorrhea, with 0 registered clinical trials and 7 publications currently retrieved. Those publications mainly cover medical abortion and do not test misoprostol as a treatment for amenorrhea, so the evidence is weak.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not stated in the Singapore licence data compiled for this report |
| Predicted New Indication | Amenorrhea |
| TxGNN Prediction Score | 99.64% |
| Evidence Level | L4 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 1 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the data compiled for this report. Based on general pharmacology, misoprostol is a prostaglandin E1 analogue. It causes uterine contraction and cervical ripening, and it also protects the gastric mucosa.
The retrieved literature concerns medical abortion (mifepristone plus misoprostol), missed abortion and abnormal uterine bleeding. Amenorrhea appears in these papers mostly as a description of gestational age (for example "amenorrhea ≤35 days"), not as a condition being treated. Misoprostol acts on the uterus and may help with retained products or pregnancy-related causes of absent menses. It has no established role in treating amenorrhea itself.
The very high TxGNN score is a computational prediction. No clinical evidence in the data supports it for this indication.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 25394644 | 2015 | Dose-ranging RCT | Reprod Sci | Lower doses of mifepristone (150 to 50 mg) followed by 200 µg oral misoprostol in 2,500 women with ultra-early pregnancy (amenorrhea ≤35 days); primary endpoint was complete abortion |
| 27678099 | 2017 | RCT | Reprod Sci | Low-dose mifepristone with self-administered misoprostol for ultra-early medical abortion; 744 women compared hospital vs self-administration |
| 26405260 | 2015 | Cohort | Hum Reprod | Low-dose mifepristone plus misoprostol before expected menstruation to maintain or restore non-pregnant status |
| 29974571 | 2018 | Cohort | J Obstet Gynaecol Res | Safety and efficacy of low-dose mifepristone with self-administered misoprostol for early pregnancy termination |
| 1486304 | 1992 | Review | BMJ | Medical management of missed abortion and anembryonic pregnancy |
| 26001691 | 2015 | Review | J Obstet Gynaecol Can | Endometrial ablation in the management of abnormal uterine bleeding |
| 37113350 | 2023 | Case report | Cureus | Acute fatty liver of pregnancy presenting with amenorrhea; not a misoprostol efficacy study |
All of these papers concern pregnancy termination or related conditions. None shows that misoprostol treats amenorrhea.
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN03501P | CYTOTEC TABLET 200 mcg | Tablet (oral) | Not specified in the data compiled |
Safety Considerations
- Contraindication signals from the knowledge graph (these come from drug-disease relationship data, not from the package insert): hypertension, liver failure or liver disease, gallbladder disease, congestive heart failure, inflammatory bowel disease, asthma, substance abuse/dependence, blood coagulation disease, stroke and cerebrovascular disorders, myocardial infarction and other cardiovascular disease, anaemia and haemoglobinopathy, drug-induced liver injury, active peptic ulcer disease, and non-infectious meningitis.
- Drug interactions: 100 interactions were found in total. The first 20 reviewed include:
- Major: dinoprostone (topical)
- Moderate: magnesium-containing antacids (magnesium oxide, magnesium carbonate, magnesium hydroxide, magaldrate) and quinapril
- Minor: sodium citrate, aluminium hydroxide, calcium carbonate, sodium bicarbonate and naproxen
- Unclassified: goserelin, cyclosporine, cyanocobalamin, calcitriol, folic acid, pravastatin, valsartan, ramipril and lorazepam
- Pregnancy-related concern: Prenatal misoprostol exposure has been associated with vascular disruption defects. Any use in women of reproductive age needs careful pregnancy exclusion.
Please refer to the package insert for the full warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The TxGNN score for amenorrhea is very high (99.64%), but no clinical trials exist and the retrieved literature is about medical abortion, not amenorrhea treatment. The package insert safety data and the mechanism of action are also missing, so the evidence is too weak to support further development for this indication.
To proceed, the following is needed:
- Singapore package insert warnings, contraindications and approved indication text
- Detailed mechanism of action data
- Clinical evidence showing that misoprostol treats amenorrhea itself
- A safety assessment for women of reproductive age, including pregnancy exclusion
Other predicted indications:
- Esophageal disease (score 96.55%, L4, "Research Question") is the more plausible candidate. Misoprostol's mucosal protective action gives a biological link, and a retrospective report describes treating idiopathic esophageal ulceration in AIDS (PMID 9820375). However, the evidence is mainly reviews plus that case-level report, and proton pump inhibitors are the standard of care.
- The remaining predictions have no clinical or literature support: atypical coarctation of aorta, aortic malformation, esophageal malformation, acne, primary hereditary glaucoma, open-angle glaucoma, congenital hypotrichosis milia, and a complex congenital heart defect. All remain at Hold.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.