Amiodarone

證據等級: L5

預測適應症: 10 個

Amiodarone: From Ventricular Arrhythmias to Catecholaminergic Polymorphic Ventricular Tachycardia

One-Sentence Summary

Amiodarone is a broad-spectrum Class III antiarrhythmic drug with multi-channel blocking properties, clinically established for the treatment of life-threatening ventricular and supraventricular arrhythmias. The TxGNN model predicts it may be effective for Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT), with 0 clinical trials and 10 publications currently supporting this direction — the majority of which describe Amiodarone as a rescue agent rather than a dedicated CPVT therapy.

Quick Overview

Item	Content
Original Indication	Ventricular arrhythmias / cardiac antiarrhythmic (Class III agent)
Predicted New Indication	Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)
TxGNN Prediction Score	99.78%
Evidence Level	L4
India Market Status	✗ Not Marketed
Number of Registrations	0
Recommended Decision	Hold

Why Is This Prediction Reasonable?

Currently, detailed mechanism of action data is not available from the regulatory database. Based on known pharmacological information, Amiodarone is a multi-channel antiarrhythmic agent that primarily prolongs the cardiac action potential by blocking K⁺ channels (IKr/IKs), while also demonstrating Na⁺ channel (use-dependent, Class I), Ca²⁺ channel (Class IV), and β-adrenergic receptor blocking (Class II) activity. This broad multi-channel profile makes it one of the most potent antiarrhythmic drugs available for suppressing reentrant circuits, abnormal automaticity, and triggered activity.

The mechanistic connection to CPVT is theoretically plausible: Amiodarone’s β-adrenergic blocking activity can attenuate catecholamine-driven calcium overload, and its Na⁺/Ca²⁺ channel blockade can suppress the triggered activity that results from delayed afterdepolarisations (DADs). Both CPVT and the indications for which Amiodarone is currently used share the common feature of life-threatening ventricular arrhythmias provoked by adrenergic stress.

However, the core pathophysiology of CPVT — mutations in the RYR2 or CASQ2 genes causing abnormal spontaneous calcium release from the sarcoplasmic reticulum — cannot be directly corrected by Amiodarone. Unlike Flecainide, which binds directly to the RYR2 channel and suppresses pathological calcium leak at its source, Amiodarone acts downstream and non-specifically. The theoretical rationale is mechanistically reasonable but lacks the target specificity required for definitive CPVT treatment, which explains the absence of dedicated clinical trials.

Clinical Trial Evidence

Currently no related clinical trials registered for Amiodarone in catecholaminergic polymorphic ventricular tachycardia.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
26513538	2015	Narrative Review	Expert Opinion on Pharmacotherapy	Comprehensive review of pharmacological treatment for ventricular arrhythmias; Amiodarone highlighted as important for both acute conversion and chronic prevention, with context for its role across arrhythmia subtypes
22553997	2012	Case Series	Pacing Clin Electrophysiol	14-year-old boy with CPVT (CASQ2 mutation) developed ICD-induced arrhythmic storm; Flecainide successfully suppressed storming where other agents (including Amiodarone context) were insufficient — highlights mechanism gap
37852665	2023	Case Report	BMJ Case Reports	Young child in out-of-hospital cardiac arrest received 40 defibrillation shocks and multimodal pharmacotherapy including Amiodarone; eventually diagnosed with CPVT — illustrates Amiodarone as acute rescue agent
17125720	2006	Case Report	Rev Española de Cardiología	CPVT patient with ICD-triggered arrhythmic storm; Amiodarone used in acute management of electrical storm, providing clinical context for its emergency role
22218697	2012	Case Report	Anesthesia & Analgesia	Neonate with long QT syndrome and refractory polymorphic VT managed with multimodal therapy including Amiodarone, esmolol and lidocaine plus ventricular pacing; demonstrates Amiodarone’s role in neonatal refractory arrhythmia
35892906	2022	Retrospective Cohort	Life (Basel)	Systematic review of CPVT patients in China — clinical characteristics, genetic basis (RYR2 vs. CASQ2), and arrhythmic outcomes; establishes disease profile and treatment landscape
39076628	2022	Registry/Database Study	Reviews Cardiovasc Med	Retrospective cohort of Chinese CPVT patients examining clinical characteristics, genetic basis, healthcare utilisation, and costs; provides real-world burden data
29668588	2018	Case Report	Medicine	9-year-old with RYR2 mutation (c.7580T>G) CPVT misdiagnosed for 6 years; highlights diagnostic delays and treatment challenges in paediatric CPVT
30116135	2018	Case Report	Turk Pediatri Arsivi	CPVT presenting as sudden cardiac arrest in a 2-year-old; detailed description of acute arrhythmia management and diagnosis in the absence of structural heart disease
39735866	2024	Case Report	Front Cardiovasc Med	Teenager with CPVT successfully managed by right cardiac sympathetic denervation after left denervation failure; illustrates the role of non-pharmacological escalation when medications are insufficient

India Market Information

Amiodarone currently has no registered products in the India market as captured in this dataset. No license records are available for review.

Note: Amiodarone is a widely used antiarrhythmic agent globally (approved in the US, EU, and many Asian markets). The absence from this dataset may reflect a data coverage gap rather than regulatory unavailability. Independent verification against the CDSCO database is recommended.

Safety Considerations

Drug Interactions: Amiodarone has an extensive drug interaction profile with 355 known interactions documented. Clinically significant interactions include:

Major interactions:

Agalsidase beta — Amiodarone may inhibit lysosomal enzyme activity, reducing efficacy of enzyme replacement therapy for Fabry disease
Hydrocortisone / Dexamethasone — Combined use may increase cardiac risk; corticosteroid-induced electrolyte disturbances (hypokalaemia) can potentiate QT prolongation
Amphotericin B (and all formulations: cholesteryl sulfate, lipid complex, liposomal) — Risk of additive hypokalaemia and QTc prolongation
Cisapride — Severe combined QT prolongation risk; concurrent use generally contraindicated
Clarithromycin — CYP3A4 inhibition increases Amiodarone plasma levels; combined QT prolongation risk
Clotrimazole — Azole antifungal CYP interaction; QTc prolongation risk
Dolasetron — 5-HT3 antagonist with QTc prolongation; additive cardiac risk
Eliglustat — CYP2D6/3A4 interaction; Amiodarone is a CYP2D6 inhibitor, increasing Eliglustat exposure significantly

Moderate interactions (selected): Famotidine, Aprepitant, Bisacodyl, Budesonide (including nasal), Castor oil, Cimetidine

Please refer to the package insert for complete warnings, contraindications, and full safety information, including thyroid toxicity (hypo/hyperthyroidism), pulmonary toxicity, hepatotoxicity, and ocular effects.

Conclusion and Next Steps

Decision: Hold

Rationale: Evidence for Amiodarone specifically in CPVT is limited to L4 (preclinical and case-report level), with no dedicated clinical trials and existing publications describing Amiodarone primarily as an acute rescue agent rather than a targeted CPVT therapy. Critically, Amiodarone does not address the core RYR2/CASQ2 calcium release defect, and more mechanism-specific agents (beta-blockers, Flecainide) are the current standard of care.

To proceed, the following is needed:

Obtain CDSCO/TFDA package insert to fill critical data gaps: formal warnings, contraindications, and approved indications (currently blocking for safety screening)
Retrieve detailed MOA from DrugBank API (DB01118) to complete mechanistic link analysis
Conduct a structured literature search specifically comparing Amiodarone versus Flecainide and beta-blockers in CPVT to determine if any subpopulation (e.g., CASQ2 vs. RYR2 genotype, refractory to first-line therapy) may benefit
Consider whether the more robustly supported indications in this report — incessant infant ventricular tachycardia (L3, Proceed with Guardrails) and ventricular tachycardia (L1, Proceed with Guardrails) — are prioritised for the India repurposing pathway before pursuing CPVT
Assess Amiodarone’s long-term toxicity profile (particularly thyroid and pulmonary effects) against the typically young/paediatric CPVT population to evaluate feasibility of chronic use

⚠️ Research Disclaimer: This report is for research reference only and does not constitute medical advice. All drug repurposing candidates require clinical validation before therapeutic application.

Disclaimer

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