Indications

Amiodarone is a potent anti-arrhythmic agent used in both ventricular and supra-ventricular tachycardias (including atrial fibrillation (AF),¹ paroxysmal AF and Wolff-Parkinson-White syndrome). Amiodarone is also used in addition to an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) to prevent structural atrial remodelling which occurs as a consequence of uncontrolled AF.

It has multiple electrophysiological effects,² but generally it is relegated to a second line drug because of a high incidence of side-effects and drug interactions. It should only be initiated under specialist supervision.

It is sometimes used for "drug cardioversion" of patients in AF, or more controversially to maintain sinus rhythm after cardioversion (where it is better than sotalol or propafenone).^1,3 It is used after adrenaline in current advanced life support (ALS) protocols in shock refractory pulseless ventricular tachycardia (VT) and ventricular fibrillation (VF).

Pharmacokinetics

Amiodarone has a structure similar to thyroxine with a high iodine content. It causes little or no myocardial suppression.⁴ It is best absorbed with food, and is highly lipid soluble, taking many days to reach a steady state if given orally, as it is taken up and stored in adipose tissue, muscle, liver, lungs and skin (large volume of distribution). Intravenous amiodarone may work more quickly and is the usual route of administration in the acute hospital situation.⁵ It takes a very long time to be eliminated from the body (half life ~58 days).² Electrophysiological studies will not usually be undertaken until amiodarone has been eliminated.

Mode of action

It is a Class III anti-arrhythmic agent (Vaughan Williams classification) as it prolongs the QT interval; but it also slows heart rate and AV node conduction (via calcium channel and beta-receptor blockade), slows intracardiac conduction (sodium channel blockade); and increases the refractory period (blocking potassium and sodium channels).

Important side-effects⁴

See drug monograph for full list.

• Pulmonary: pulmonary fibrosis. Pneumonitis - chronic cough, breathlessness and interstitial infiltrates on CXR. Occasionally causes Adult Respiratory Distress Syndrome (separate record).
• Cardiac: bradycardia and heart block. It should not be used in patients with second- or third-degree heart block who do not have a pacemaker, or pacing readily available. Rarely causes torsades de pointes ventricular tachycardia.
• Ophthalmic: most patients develop reversible corneal microdeposits - visible on slit lamp (and which occasionally produce difficulties driving at night). Optic neuropathy and optic neuritis have been reported (note any changes in acuity or peripheral fields).
• Thyroid dysfunction: an isolated raised T4, hyperthyroidism or hypothyroidism can all occur. Hypothyroidism is normally treated with levothyroxine, and the drug can be continued if essential.² See separate record Hypothyroidism. Hyperthyroidism is more difficult to treat and usually requires stopping of amiodarone and antithyroid medication may be needed (e.g. carbimazole).⁴ See separate record Hyperthyroidism (Thyrotoxicosis).
• Skin: photosensitivity is common - warn patients to use wide spectrum sunblocks (protecting against visible and UV light) whilst on treatment and for some months afterwards. Grey/blue temporary skin discolouration may occur whilst on treatment.
• Liver: hepatoxicity can occur necessitating discontinuation of drug. Cirrhosis has been reported.^6,7
• Neurotoxicity: including tremor, gait problems and cognitive impairment are probably less frequent than originally thought.⁸

Important drug interactions

See drug monograph for full list.

• Warfarin - reduce warfarin dose by half and monitor INR regularly.
• Digoxin - reduce digoxin dose and monitor drug levels.
• Simvastatin - increased likelihood of myopathy (if simvastatin >20 mg/day).⁹
• Additive affects other antiarrhythmics (see individual drug records for details).
• Quinolones and other drugs which affect QT interval (increased risk of arrhythmias).

Before initiation

Where possible:

• Check baseline thyroid function, liver enzymes.
• Regular INR tests (at least weekly for first 6 weeks) if on warfarin.
• Consider baseline CXR and lung function tests if previous lung disease.
• Arrange ophthalmological examination (if there is any pre-existing visual impairment).

Monitoring

• Thyroid function tests 6-monthly (T4, T3 and TSH).¹⁰
• Liver function tests (transaminases) every 6 months.
• INR regularly if on warfarin; digoxin level may also be helpful.
• Review regularly to assess heart rate, heart rhythm control, any heart failure and to check for side-effects and possible interactions.
• Warn patients to limit sunlight exposure and to use a sunscreen.¹¹
• Ophthalmic assessment if any change in visual acuity or visual fields.² Some recommend annual slit lamp examination.¹²