Dronedarone

Classification:

Amiodarone – the most effective anti-arrhythmic drug, but associated with the highest rate of adverse effects.
Dronedarone – similar to amiodarone, but less potent and associated with fewer adverse effects.
Sotalol – also a non-selective beta-blocker.
Ibutilide – may be used for acute cardioversion of pre-excited atrial fibrillation (AF).

Mechanism:

Dronedarone is a “modified amiodarone”; it is less potent and associated with fewer adverse effects than amiodarone.
Predominantly exhibits Class III properties, but also Class I, II, and IV effects

Prolongs the effective refractory period (ERP) in atrial and ventricular myocardium

Effect on AF:

Dronedarone and atrial fibrillation (AF)
Brand name
Multaq
Indications
Maintenance of sinus rhythm
Dosing
Chronic rhythm control – maintenance of sinus rhythm (oral) 400 mg twice daily
Onset of action
3–6 hours (oral)
Effect
Maintenance of sinus rhythm (paroxysmal or persistent AF) at 1 year 30–40 %
Duration of action
12–24 hours (oral)
Contraindications
Permanent atrial fibrillation (when sinus rhythm cannot be restored) QTc interval ≥ 500 ms PR interval > 280 ms Current or previous cardiac decompensation Chronic heart failure (NYHA III, IV) HFrEF < 40 % Second- or third-degree AV block (without pacemaker) Sick sinus syndrome (without pacemaker) Bradycardia < 50/min Pulmonary toxicity after amiodarone Hepatotoxicity after amiodarone Severe hepatic impairment Allergy to dronedarone Concomitant use of erythromycin Concomitant use of strong CYP3A4 inhibitors e.g. ketoconazole, itraconazole, voriconazole, ciclosporin, clarithromycin, ritonavir Concomitant use of QT-prolonging drugs e.g. tricyclic antidepressants, macrolides, Class I and III anti-arrhythmic drugs

Patient monitoring after initiation of dronedarone:

Patient monitoring before and during dronedarone therapy
Time	What to monitor	Reason for discontinuation
Before initiation	ECG (QTc interval, AV block) Liver tests (ALT, AST, GGT, ALP, bilirubin)	QTc ≥ 500 ms Second- or third-degree AV block Abnormal liver tests
2 months	Liver tests ECG	Marked deterioration of liver tests QTc interval ≥ 500 ms PR interval > 280 ms
4 months	Liver tests ECG	Marked deterioration of liver tests QTc interval ≥ 500 ms PR interval > 280 ms
6 months	Liver tests ECG	Marked deterioration of liver tests QTc interval ≥ 500 ms PR interval > 280 ms
Every 1 year	Liver tests ECG Echocardiography	Marked deterioration of liver tests QTc interval ≥ 500 ms PR interval > 280 ms Ejection fraction < 40%

Adverse effects:

Amiodarone and dronedarone both belong to Class III anti-arrhythmic drugs but differ in their properties.

Amiodarone vs dronedarone and atrial fibrillation
Property	Amiodarone	Dronedarone
Efficacy (maintenance of SR)	60–70 % at 1 year	30–40 % at 1 year
Onset of action	Slow (days–weeks, full effect after loading of ~10 g)	Faster (3–6 hours)
Duration of action	Persists 2–3 months after discontinuation	12–24 hours (disappears after dose omission)
Suitable patient	Also with structural heart disease	Patient without structural heart disease and with preserved ejection fraction
Heart failure	May be used (including HFrEF)	Contraindicated (NYHA III–IV, HFrEF < 40 %)
Tissue accumulation	Yes – adipose tissue, lungs, eye, thyroid gland	Minimal
Lungs (toxicity)	Pulmonary fibrosis, interstitial pneumonitis	No pulmonary toxicity
Liver (toxicity)	Mild hepatotoxicity, elevated liver enzymes	Possible severe hepatitis, hepatic failure
Thyroid (toxicity)	Hypothyroidism and hyperthyroidism	No effect on the thyroid gland
Eyes (toxicity)	Corneal deposits, optic neuropathy	No ocular toxicity
Skin (toxicity)	Photosensitivity, blue-grey skin discoloration	Skin rash, pruritus