19774-82-4

Therapeutic Function

Coronary vasodilator

Biochem/physiol Actions

Non-selective ion channel blocker with broad fungicidal activity. Amiodarone induces an immediate influx of Ca2+ in Saccharomyces cerevisiae, followed by mitochondrial fragmentation and cell death.

Veterinary Drugs and Treatments

Because of its potential toxicity and lack of experience with use in canine and equine patients, amiodarone is usually used when other less toxic or commonly used drugs are ineffective. It may be useful in dogs and horses to convert atrial fib into sinus rhythm and in dogs for arrhythmias associated with left ventricular dysfunction. In horses, one horse with Ventricular tachycardia was converted into sinus rhythm using amiodarone. As the risk of sudden death is high in Doberman pinschers exhibiting rapid, wide-complex ventricular tachycardia or syncope with recurrent VPC’s, amiodarone may be useful when other drug therapies are ineffective.

Drug interactions

Potentially hazardous interactions with other drugs Anti-arrhythmics: additive effect and increased risk of myocardial depression; increased risk of ventricular arrhythmias with disopyramide or dronedarone - avoid; increased flecainide concentration - halve flecainide dose; increased procainamide concentration - avoid. Antibacterials: increased risk of ventricular arrhythmias with parenteral erythromycin, cotrimoxazole levofloxacin and moxifloxacin - avoid; increased risk of ventricular arrhythmias with delamanid; avoid with fidaxomicin; possibly increased risk of ventricular arrhythmias with telithromycin. Anticoagulants: metabolism inhibited (increased anti-coagulant effect); increased dabigatran concentration (reduce dabigatran dose). Antidepressants: increased risk of ventricular arrhythmias with citalopram and escitalopram, tricyclic antidepressants and venlafaxine - avoid. Antiepileptics: phenytoin and fosphenytoin metabolism inhibited (increased concentration). Antifungals: avoid with fluconazole due to risk of QT prolongation. Antihistamines: increased risk of ventricular arrhythmias with mizolastine - avoid. Antimalarials: increased risk of ventricular arrhythmias with chloroquine, hydroxychloroquine, mefloquine and quinine and possibly with piperaquine with artenimol and artemether/ lumefantrine - avoid. Antimuscarinics: increased risk of ventricular arrhythmias with tolterodine. Antipsychotics: increased risk of ventricular arrhythmias with antipsychotics that prolong the QT interval; increased risk of ventricular arrhythmias with amisulpride, benperidol, droperidol, haloperidol, phenothiazines, pimozide or zuclopenthixol - avoid; increased risk of ventricular arrhythmias with sulpiride. Antivirals: increased risk of ventricular arrhythmias with fosamprenavir ritonavir, saquinavir and telaprevir - avoid; concentration possibly increased by atazanavir; possible increased risk of bradycardia with daclatasvir, ledipasvir, sofosbuvir and simeprevir; avoid with indinavir, reduce the dose of the others. Atomoxetine: increased risk of ventricular arrhythmias. Beta-blockers, diltiazem, and verapamil: increased risk of bradycardia, AV block and myocardial depression; increased risk of ventricular arrhythmias with sotalol - avoid. Ciclosporin: increased levels of ciclosporin possible. Cobicistat: concentration possibly increased by cobicistat - avoid. Colchicine: possibly increased colchicine toxicity. Cytotoxics: possibly increased afatinib concentration (separate administration by 6-12 hours); possibly increased risk of ventricular arrhythmias with panobinostat and vandetanib - avoid; concentration of ibrutinib possibly increased - reduce dose of ibrutinib; avoid with idelalisib; increased risk of ventricular arrhythmias with arsenic trioxide, bosutinib and ceritinib. Digoxin: increased concentration (halve digoxin maintenance dose). Fingolimod: possible increased risk of bradycardia. Grapefruit juice: may increase concentration of amiodarone - avoid. Ivabradine: increased risk of ventricular arrhythmias - avoid. Lipid-lowering drugs: give lomitapide 12 hours after amiodarone; increased risk of myopathy with simvastatin - do not exceed 20 mg of simvastatin.1 Lithium: increased risk of ventricular arrhythmias - avoid. Pentamidine: increased risk of ventricular arrhythmias - avoid.

Metabolism

Amiodarone is metabolised in the liver; the major metabolite, desethylamiodarone, also has antiarrhythmic properties. There is very little urinary excretion of amiodarone or its metabolites, the major route of excretion being in faeces via the bile; some enterohepatic recycling may occur.

General Description

Amiodarone, marketed as Pacerone?, Cordarone?, Aratac, and Atlansil, is an antiarrhythmic agent monitored by clinical labs using HPLC or LCMS to ensure patients remain within the drugs therapeutic range.