Amiodarone
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
- Amiodarone
- Amiodarone: From Ventricular Fibrillation to Catecholaminergic Polymorphic Ventricular Tachycardia
Amiodarone: From Ventricular Fibrillation to Catecholaminergic Polymorphic Ventricular Tachycardia
One-Sentence Summary
Amiodarone is a multichannel antiarrhythmic originally used for ventricular fibrillation. The TxGNN model predicts it may be effective for Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT), but the data compiled for this report show no clinical trials and only 9 publications, mostly case reports and disease descriptions rather than studies of amiodarone efficacy. Among the other predictions, ventricular tachycardia (18 clinical trials, 20 publications) and incessant infant ventricular tachycardia (19 publications, including one RCT) have far stronger support, and they are discussed in the conclusion.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Ventricular fibrillation (the Singapore licence records contain no approved indication text) |
| Predicted New Indication | Catecholaminergic polymorphic ventricular tachycardia (CPVT) |
| TxGNN Prediction Score | 99.78% |
| Evidence Level | L4 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 3 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on known information, amiodarone blocks potassium, sodium and calcium channels and also has beta-adrenergic blocking activity. It prolongs the action potential and refractory period, and its efficacy in ventricular arrhythmias such as ventricular fibrillation is established.
CPVT is an inherited arrhythmia caused by calcium-handling abnormalities (RYR2/CASQ2 mutations) that produce adrenergically triggered ventricular arrhythmias. Amiodarone's beta-blocking and calcium-channel-blocking activity gives a plausible but indirect rationale.
The rationale is weak, however. Beta-blockers (nadolol) and flecainide are the standard of care, and amiodarone is generally considered ineffective or only adjunctive in CPVT. The retrieved literature describes the disease and does not demonstrate amiodarone efficacy. The prediction should therefore be treated as a research question.
Clinical Trial Evidence
Currently no related clinical trials registered for CPVT.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 35892906 | 2022 | Systematic review | Life (Basel) | Clinical characteristics, genetics and arrhythmic outcomes of CPVT patients from China |
| 39076628 | 2022 | Cohort | Rev Cardiovasc Med | CPVT characteristics, genetics, healthcare use and costs in a Chinese city |
| 26513538 | 2015 | Review | Expert Opin Pharmacother | Role of antiarrhythmic drugs in acute conversion and chronic prevention of ventricular arrhythmias |
| 22553997 | 2012 | Case report | Pacing Clin Electrophysiol | Flecainide suppressed defibrillator-induced storming in CPVT (not amiodarone) |
| 39735866 | 2024 | Case report | Front Cardiovasc Med | Right cardiac sympathetic denervation resolved CPVT in a teenager after left denervation |
| 29668588 | 2018 | Case report | Medicine | Delayed diagnosis of CPVT with an RYR2 mutation in a 9-year-old child |
| 30116135 | 2018 | Case report | Turk Pediatri Arsivi | CPVT presenting as sudden cardiac arrest in a 2-year-old |
| 37852665 | 2023 | Case report | BMJ Case Reports | Young child with out-of-hospital cardiac arrest and recurrent VT/VF requiring deviation from standard resuscitation |
| 22218697 | 2012 | Case report | Anesth Analg | Neonate with long QT syndrome and refractory ventricular arrhythmias treated with several drugs including amiodarone |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN15782P | DIOLUX Concentrate for Solution for Injection 50 mg/ml | Injection, solution, concentrate | Not stated in the data |
| SIN09784P | CORDARONE Tablet 200 mg | Tablet | Not stated in the data |
| SIN00852P | CORDARONE Injection 150 mg/3 ml | Injection | Not stated in the data |
Safety Considerations
- Contraindications / disease associations (knowledge-graph derived, not label text): Long QT syndrome (including familial), torsades de pointes, atrioventricular block, sick sinus syndrome, hypothyroidism and hyperthyroidism (including Graves disease, thyrotoxicosis, myxedema), liver disease and drug-induced liver injury, interstitial lung disease, eosinophilic pneumonia, hypersensitivity pneumonitis, peripheral neuropathy, optic neuritis and optic nerve disease, corneal deposits, potassium deficiency, and gallbladder disease.
- Drug Interactions: 100 interactions were identified. Major interactions in the data include amphotericin B (several formulations), cisapride, clarithromycin, clotrimazole, dexamethasone, hydrocortisone, dolasetron, eliglustat and agalsidase beta. Moderate interactions include famotidine, cimetidine, aprepitant, bisacodyl, budesonide and castor oil.
For label-based warnings and contraindications, please refer to the package insert.
Conclusion and Next Steps
Decision: Hold (for CPVT)
Rationale: There are no clinical trials for CPVT, and the literature consists of disease descriptions and case reports. Standard therapies (beta-blockers, flecainide) are established, and amiodarone is considered ineffective or only adjunctive. The evidence level is L4.
Other predictions in the data:
- Ventricular tachycardia (L1, Proceed with Guardrails): This is largely an on-label or near-label use rather than true repurposing. The data include completed Phase 3 trials (ALPS, n=3,024; AVID) and a randomized comparison with procainamide (PROCAMIO). Guardrails are monitoring for pulmonary, thyroid and hepatic toxicity and QT prolongation, and managing the many drug interactions.
- Incessant infant ventricular tachycardia (L2, Proceed with Guardrails): Supported by a randomized double-blind pediatric trial of IV amiodarone (Circulation 2005) and infant cohorts, but this evidence mostly covers incessant tachyarrhythmias in general, including supraventricular, rather than infant VT specifically. Guardrails are infant-specific dosing, thyroid effects from the iodine load, QT and proarrhythmia monitoring, and pediatric cardiology oversight.
- Obsolete bundle branch block, rheumatoid arthritis, brachydactyly-syndactyly syndrome, heparin cofactor 2 deficiency, trichotillomania, colobomatous microphthalmia-rhizomelic dysplasia syndrome, gout (all L5, Hold): No credible mechanistic link or supporting studies. The high scores likely reflect knowledge-graph artifacts. For rheumatoid arthritis, the literature points to amiodarone pulmonary toxicity as a safety concern.
To proceed, the following is needed:
- Mechanism of action data (MOA)
- Package insert warnings and contraindications from the HSA, to complete the safety screening
- For CPVT: comparative or controlled data on amiodarone against nadolol or flecainide before any further evaluation
- Approved indication text for the three Singapore licences, to confirm the original and current labelled uses
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.