Midodrine
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Midodrine: Variably protease-sensitive prionopathy
One-Sentence Summary
Midodrine is a peripheral alpha-1 adrenergic agonist, originally used for orthostatic hypotension, multiple system atrophy and postural orthostatic tachycardia syndrome. The TxGNN model predicts it may be effective for hypotensive disorder, supported by 1 clinical trial (Phase 2) and 18 publications. This predicted indication largely overlaps with the drug’s existing use, so it is better viewed as confirmation than as true repurposing.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Variably protease-sensitive prionopathy |
| TxGNN Prediction Score | 0.9999 |
| Evidence Level | L5 |
| Canada Market Status | Marketed (marketed DINs: 10 of 10) |
| Number of DINs | 10 (marketed: 10) |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the data compiled for this report. Based on known information, midodrine is a prodrug whose active metabolite, desglymidodrine, is a peripheral alpha-1 agonist. It causes arterial and venous vasoconstriction and raises blood pressure.
Its efficacy in orthostatic hypotension is established, and the same blood-pressure-raising effect is mechanistically applicable to other hypotensive states, such as hypotension secondary to spinal cord injury or other conditions. A 1989 review in Drugs describes midodrine’s use in orthostatic hypotension and secondary hypotensive disorders.
Because the predicted indication is close to the original one, the link is strong and direct. This is a confirmation of existing use, not a new therapeutic area.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT02893553 | Phase 2 | Completed | 21 | Effects of normalizing blood pressure on cerebral blood flow in hypotensive individuals with spinal cord injury. The trial is small and focused on cerebral blood flow outcomes. |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 25644760 | 2015 | Randomized trial | Hepatology | Terlipressin plus albumin compared with midodrine and octreotide plus albumin in hepatorenal syndrome |
| 2480881 | 1989 | Review | Drugs | Midodrine pharmacology and use in orthostatic hypotension and secondary hypotensive disorders |
| 38123372 | 2024 | Review | Revue neurologique | Expert position statement on orthostatic hypotension |
| 38205630 | 2024 | Scientific statement | Hypertension | American Heart Association statement on orthostatic hypotension in adults with hypertension |
| 28050656 | 2017 | Consensus recommendations | Journal of neurology | Screening, diagnosis and treatment of neurogenic orthostatic hypotension and supine hypertension |
| 32979782 | 2020 | Review | Autonomic Neuroscience | Pharmacologic treatment of neurogenic orthostatic hypotension |
| 41941194 | 2026 | Review | JAMA Internal Medicine | Management of orthostatic hypotension |
| 42635998 | 2026 | Review | JAMA | Review of postural orthostatic tachycardia syndrome |
| 31996627 | 2020 | Review | Continuum | Management of orthostatic hypotension, with emphasis on neurogenic forms |
| 37978969 | 2024 | Expert review | Gastroenterology | AGA update on vasoactive drugs and intravenous albumin in cirrhosis |
Canada Market Information
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 02473984 | MAR-MIDODRINE | Not listed | Not listed |
| 02473992 | MAR-MIDODRINE | Not listed | Not listed |
| 02517701 | JAMP MIDODRINE | Not listed | Not listed |
| 02547112 | M-MIDODRINE | Not listed | Not listed |
| 02533219 | MIDODRINE | Not listed | Not listed |
Ten single-ingredient DINs are currently valid and none are cancelled. Only the first five are shown here.
Safety Considerations
- Contraindications suggested by the knowledge graph (not taken from label text): pheochromocytoma (adrenal and sympathetic paraganglioma), thyrotoxicosis, hyperthyroidism, Graves disease, and several cancers (duodenum, small intestine, heart, adrenal gland).
- Drug Interactions: 81 interactions are recorded. Examples listed as moderate include epinephrine, ephedrine, phentermine, diethylpropion, bupropion, sibutramine, mazindol, isometheptene, lorcaserin, trospium and rolapitant. Examples listed as minor include ranitidine, cimetidine and metformin.
- Points to watch: the analysis flags supine hypertension, urinary retention and bradycardia. It also flags caution with other vasoconstrictors, beta-blockers and cardiac glycosides.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: The mechanism is direct and consistent with midodrine’s established use. A completed Phase 2 trial and several reviews and guideline-type documents support it. No Phase 3 randomized trial was identified, and the indication substantially overlaps with existing use.
To proceed, the following is needed:
- Health Canada package insert warnings and contraindications, which are currently missing and block safety screening
- Detailed mechanism of action data
- Approved indication text and dosage forms for the Canadian licences
- Evidence from Phase 3 randomized trials in specific hypotensive populations, such as spinal cord injury
- A safety monitoring plan covering supine hypertension, bradycardia and urinary retention
Other predictions: The other nine predictions have no meaningful evidence and are on Hold. These are variably protease-sensitive prionopathy, faciodigitogenital syndrome, ADHD (two entries), sinoatrial node disease, monogenic obesity, specific developmental disorder, obsolete hypertelorism and sinoatrial block. Most appear to be TxGNN model (deep learning) artifacts. For the two sinoatrial conditions, midodrine’s reflex bradycardia is a safety concern rather than a therapeutic opportunity.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.