Amiodarone

Amiodarone is a medication used to treat atrial fibrillation and ventricular tachycardia.It is the most effective agent to control heart arrhythmia; but is also the medication associated with the most frequent and significant side effects.

Mechanism

Amiodarone affects many different electrical proteins in the heart. The combined effect is to slow the heart beat, reduce the ‘excitability’ of the heart, and so to suppress atrial fibrillation and ventricular arrhythmia (ventricular tachycardia and fibrillation).

Dosing

Amiodarone may be given orally or as an intravenous medication. When given orally, it is typically started at a high dose - 200-400mg three times a day for 5-7 days - then reduced to 100-200mg a day thereafter. Higher doses may be used if arrhythmia recurs.

Side Effects

Unfortunately, amiodarone is associated with frequent, significant, side effects/complications including:

• Lung: Interstitial pneumonitis or fibrosis (~1%)
• Thyroid: Both over and underactive thyroid (5-10%)
• Liver: Hepatotoxicity.
• Heart: Bradycardia, AV block (2-3%)
• Ocular: Corneal micro-deposits, optic neuropathy or neuritis (causing visual loss).
• Dermatologic: Blue-grey skin discolouration which is irreversible.
• Neurologic: Peripheral neuropathy.

Complications are more common at higher doses (>200-300mg a day), but can occur at any dose if given for long enough.

Monitoring

Due to the high rate of complications on this medication, if continued in the medium to long-term (months to years) it is important to monitor closely.

At baseline, an echocardiogram, ECG, and blood tests - TFT (thyroid), LFT (liver), and EUC (kidney) are performed.

It is important for every patient on amiodarone to report new cough, increasing shortness of breath, any fainting episode, or loss of vision. You will also be asked about these symptoms at each clinic visit.

The blood tests and ECG will be repeated at 6 monthly intervals, and specific testing is performed (such as lung function testing, or CXRAY, or eye examination) if symptoms develop.

Drug Interactions (Advanced)

Amiodarone has numerous drug interactions. The list that follows includes some of the commonly co-administered drugs, though every new medication should be checked for an interaction with amiodarone.

1. Warfarin (Coumadin): amiodarone increases the effect; the dose of warfarin may need to be reduced while you are on amiodarone.

2. Dabigatran (Pradaxa): amiodarone increases dabigatran levels; amiodarone is best used with an alternative oral anticoagulant such as apixaban.

3. Digoxin (Lanoxin): Amiodarone increases serum digoxin levels, which can lead to digoxin toxicity. The digoxin dose may need to be reduced.

4. Statins (e.g., Simvastatin, Atorvastatin, Rosuvastatin): Risk of myopathy or rhabdomyolysis may increase when these are taken with amiodarone. It is reasonable to take them together, but careful monitoring is required. Simvastatin should not be used at a dose above 20mg a day.

5. CYP3A4 substrates: Amiodarone inhibits the CYP3A4 enzyme, which can increase the levels of many drugs, including cyclosporine, sildenafil, and certain antifungals like itraconazole.

6. Grapefruit Juice: May increase amiodarone level.

Summary

Amiodarone is both the most effective and most troublesome medication used to treat heart rhythm abnormalities.

In the short term (weeks-months), with an unstable rhythm, amiodarone is an excellent medication, with a low risk of complication. In the medium to long term the increasing risk of serious complication necessitates a careful consideration of the benefits and risks of therapy, and consideration of alternative treatments (such as catheter ablation, or an alternative antiarrhythmic medication) which may be able to achieve the same effect but at lower risk.