Amiodarone

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).

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 fibrillation (VF).

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 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

It is a Class III anti-arrhythmic agent (Vaughan Williams classification) as it prolongs the Q-T interval; but it also slows heart rate and A-V 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).

See drug monograph for full list.

• Pulmonary: Pulmonary fibrosis. Pneumonitis - chronic cough, breathlessness and interstitial infiltrates on CXR. Occasionally causes adult respiratory distress syndrome.
• 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 has 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 essential². Hyperthyroidism is more difficult to treat and usually requires the stopping of amiodarone and antithyroid medication may be needed (eg carbimazole).⁴
• Skin Photosensitivity is common - warn patients to use wide spectrum sun blocks (protecting against visible and UV light) whilst on treatment and for some months afterwards. Grey/blue temporary skin discoloration may occur whilst on treatment.
• Liver: hepatoxicity can occur necessitating discontinuation of drug. Cirrhosis has been reported.⁶

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 >20mg/day).
• Additive affects other antiarrhythmics (see individual drug records for details).
• Quinolones and other drugs which affect QT interval (increased risk of arrhythmias).

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).

• Thyroid function tests 6 monthly (T4, T3 and TSH)
• 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.⁷
• Ophthalmic assessment if any change in visual acuity or visual fields.² Some recommend annual slit lamp examination.⁸