Amiodarone: Uses, Preparations
Uses and Administration
Amiodarone is an antiarrhythmic with mainly class III properties. It is used in the control of ventricular and supraventricular arrhythmias, including arrhythmias associated with Wolff-Parkin son-White syndrome. It has been tried for the prevention of arrhythmias in patients with myocardial infarction or heart failure.
Amiodarone hydrochloride is given orally in initial doses of 200 mg three times daily for a week, then 200 mg twice daily for a week, and then a usual maintenance dosage of 200 mg or less daily, according to response. In the USA, amiodarone is only licensed for ventricular arrhythmias and higher doses are used: loading doses of amiodarone hydrochloride are up to 1.6 g daily for 1 to 3 weeks, followed by 600 to 800 mg daily for a month, then a usual maintenance dose of 400 mg daily. Consideration should be given to potential adverse effects, and patients should be given the minimum effective dose.
Amiodarone hydrochloride may be given intravenously where facilities for close monitoring of cardiac function and resuscitation are available. It is usually given as a dilute solution in glucose 5%. Solutions containing less than 600 micrograms/mL are unstable but high concentrations are irritating to the veins, and solutions containing more than 2 mg/mL should be given via a central catheter; a central catheter is also preferred if repeated or continuous infusion is required. The usual dose is 1 to 1.2 g over 24 hours, given by intermittent or continuous infusion as follows:
• in the UK, an initial infusion of 5 mg/kg in 250 mL of glucose 5% is given over 20 to 120 minutes; the infusion may be repeated if required, up to a total dose of 1.2 g in 24 hours, diluted in up to 500 mL of glucose 5%
• in the US, an initial dose of 150 mg in 100 mL of glucose 5% is given over 10 minutes, followed by 900 mg in 500 mL of glucose 5% over 24 hours, given at a rate of 1 mg/minute for 6 hours and then 500 micrograms/minute for 18 hours; if necessary the maintenance infusion may be continued at a rate of 500 micrograms/minute using a 1 to 6 mg/mL solution
• In emergencies, amiodarone hydrochloride may be given in doses of 150 to 300 mg in 10 to 20 mL of glucose 5% by slow intravenous injection over a period of not less than 3 minutes; a second injection should not be given until at least 15 minutes after the first
For the use of amiodarone in children, see below.
Administration. Addition of amiodarone hydrochloride to an intravenous infusion solution reduces the drop size delivered and the reduction in size is greater as the concentration of amiodarone is increased. This resulted in a reduction of about 30% in the expected delivery rate when amiodarone hydrochloride 1.2 g was given in 500 mL of glucose 5%. The reduction in drop size has been attributed to a reduction in surface tension caused by inclusion of Tween 80 (polysorbate 80) in the commercial injection. Allowances should be made for the changes in drop size causing a reduction of the delivery rate of infusions of amiodarone hydrochloride. US licensed product information contra-indicates the use of drop-counter infusion sets and requires the use of a volumetric infusion pump when intravenous amiodarone is given.
Administration in children. Amiodarone has been used orally and intravenously in infants and children although use of the injection is generally contra-indicated in neonates because of the presence of benzyl alcohol, a preservative that has been associated with fatalities in neonates due to the ‘gasping syndrome’ (see Neonates, under Benzyl Alcohol) and may cause adverse effects in children up to 3 years old. In the management of cardiac arrhythmias, amiodarone hydrochloride may be given orally in a loading dose of 10 to 20 mg/kg daily (or 500 mg/m daily) for 7 to 10 days, followed by the lowest possible maintenance dose, ranging from 5 to 10 mg/kg daily (or 250 mg/m daily) according to response. It has also been given intravenously in a loading dose of 5 mg/kg given over 20 minutes to 2 hours, followed by a maintenance dose of 10 to 15 mg/kg daily. The BNFC suggests intravenous doses of 5 mg/kg given over 30 minutes and repeated every 12 to 24 hours for neonates, and 5 to 10 mg/kg given over 20 minutes to 2 hours and followed by continuous infusion of 300 micrograms/kg per hour (maximum 1.5 mg/kg per hour) for infants and children.
Advanced cardiac life support. Cardiac arrest should be treated by starting full life support measures (see Advanced Cardiac Life Support). Amiodarone may be considered in cardiac arrest due to ventricular fibrillation or pulseless ventricular tachycardia that is refractory to rapid defibrillation. Although higher doses have been used, guidelines now recommend an intravenous dose of 300 mg, with a further dose of 150 mg if necessary; it may be given by intraosseous injection if the intravenous route is not available. In the UK and European guidelines, this may be followed by an infusion of 900 mg over 24 hours. A study in patients with cardiac arrest outside hospital found that amiodarone improved survival to admission, while another study found that it was more effective than lidocaine in this setting. Retrospective studies of its use in cardiac arrest occurring in hospital, however, have not found it to be of benefit.
Cardiac arrhythmias. Amiodarone is an effective drug for the treatment of symptomatic supraventricular and ventricular arrhythmias; it has a relatively low risk of cardiovascular adverse effects and may be particularly useful in patients with structural heart disease. It is also used to prevent recurrence of both supraventricular and ventricular arrhythmias, although non-cardiac toxicity may limit its long-term use; a small study suggested that short-term use (4 weeks) delayed the recurrence of atrial fibrillation after electrical cardioversion, but the benefits of this approach require confirmation in larger studies. Amiodarone has been used in children (see above), and has been given by various routes to terminate fetal arrhythmias. Perioperative use reduces the incidence of atrial fibrillation and other arrhythmias after cardiac surgery. Amiodarone may also have a role in the management of cardiac arrest (see Advanced Cardiac Life Support, above); it has been tried for its antiarrhythmic effect in the management of heart failure (see below).
Amiodarone has been used for the prevention of sudden cardiac death in patients with asymptomatic ventricular arrhythmias following myocardial infarction, in patients with a history of aborted sudden cardiac death, and in patients with hypertrophic cardio-myopathy or other cardiac disorders that place them at high risk. Although amiodarone may reduce mortality the effect appears to be small, and early use of high doses after myocardial infarction may be detrimental. For long-term prophylaxis, implantable cardioverter defibrillators are more effective than antiarrhythmic drugs and are usually preferred; amiodarone may have a role as an adjunct to implantable cardioverter defibrillators to prevent frequent shocks, and may also be used in patients who cannot be given an implantable cardioverter defibrillator.
While amiodarone can cause torsade de pointes it appears to do so rarely and patients who have had this form of ventricular tachycardia as a result of other antiarrhythmic therapy have been given amiodarone subsequently without a recurrence.
Heart failure. Sudden deaths in patients with severe heart failure have been attributed to ventricular arrhythmias but routine use of antiarrhythmics is not recommended since many have a negative inotropic effect. Amiodarone, which is not a negative inotrope, is usually the drug of choice in patients with heart failure and symptomatic arrhythmias, but its role for prophylaxis is less clear. In the GESICA study (Grupo de Estudio de la Sobrevida en la Insuficiencia Cardiaca en Argentina) amiodarone appeared to reduce mortality in patients with severe chronic heart failure who were without symptomatic ventricular arrhythmias. The decrease in mortality appeared to be greater than could be expected from antiarrhythmic activity alone. However, in the CHF-STAT study (Survival Trial of Antiarrhythmic Therapy in Congestive Heart Failure) involving patients with heart failure and premature ventricular contractions, overall survival did not appear to be improved by amiodarone. A meta-analysis including these and 3 further studies concluded that amiodarone reduced the rate of arrhythmic or sudden death in high-risk patients and that this resulted in an overall reduction in mortality. However a further study found that amiodarone had no effect on long-term survival, whereas implantable cardioverter defibrillators reduced mortality by 23%, and a retrospective analysis of a study in patients with heart failure after acute myocardial infarction found that mortality was higher in those taking amiodarone. Although some studies have suggested that amiodarone may also improve cardiac function, adverse effects limit its use, and it is not currently recommended in heart failure except in patients with symptomatic ventricular arrhythmias.
Preparations
British Pharmacopoeia, 2008: Amiodarone Intravenous Infusion; Amiodarone Tablets.
Proprietary Preparations
Argentina: Amiocar; Angoten; Asulblan; Atlansil; Coronax; Coronovo; Miodarona; Miotenk; Ritmocardyl;
Australia: Aratac; Cardinorm; CordaroneX; Rithmik
Austria; Sedacoron;
Belgium: Cordarone;
Brazil: Amiobal; Amioron †; Ancoron; Angiodarona; Angytorr †; Atlansil; Cardicoron; Cor Nio-F; Diodarone; Miocoron; Miodarid; Miodaron;
Canada: Cordarone;
Chile: Atlansil; Cordarone; Ritmocardyl;
Czech Republic: Amiohexal; Amiokordin; Cordarone; Ritmopuls; Rivodaron; Sedacoron;
Denmark: Cordan; Cordarone;
Finland: Cordarone;
France: Corbionax; Cordarone;
Germany: Amiobeta-F; Amiod-F; Amiodarex; Amiodura; Amiogamma; Amiohexal; Cordarex; Cornaron; Tachydarcing;
Greece: Angoron;
Hong Kong: Cordarone; Sedacoron;
Hungary: Amiokordin †; Cordarone; Sedacoron;
India: Aldarone-F; Cordarone; Eurythmic;
Indonesia: Cordarone; Kendaron; Tiaryt;
Ireland: Cordarone X;
Israel: Amiodacore; Pro-cor;
Italy: Amiodar; Cordarone;
Japan: Ancaron;
Malaysia: Aratac; Cordarone;
Mexico: Braxan; Cardiorona †; Cordarone; Forken; Keritmon; Sinarona;
The Netherlands: Cordarone;
Norway: Cordarone;
New Zealand: Aratac; Cordarone X;
Philippines: Cordarone;
Poland: Amiokordin; Cordarone; Opacorden;
Portugal: Corbionax; Cordarone; Miodrone;
Russia: Amiokordin; Cardiodarone; Cordarone; Rhythmiodarone; Sedacoron;
South Africa; Arycor; Cordarone X; Hexarone;
Singapore: Aratac; Cordarone;
Spain: Trangorex;
Sweden: Cordarone;
Switzerland: Amiodar; Cordarone; Escodarone; Rivodarone †;
Thailand: Amdarone; Amidarone 200; Aratac; Cordarone;
Turkey: Cordarone;
United Arab Emirates (UAE): Amirone;
United Kingdom (UK): Amyben; Cordarone X;
United States of America (US and USA): Cordarone; Pacerone;
Venezuela: Arycor; Coradona; Diarona; Eudarona; Novarona; Trangorex.
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