Propafenone

Propafenone is a class IC antiarrhythmic with mild beta blocking activity. It prevents paroxysmal atrial fibrillation and supraventricular tachycardia in patients without structural heart disease, and it can convert recent onset atrial fibrillation. Like flecainide, it is dangerous in coronary disease, after infarction, and in heart failure. It is not widely stocked in East Africa.

Classification. Class IC antiarrhythmic (sodium channel blocker with weak beta blocking and calcium channel effects).

Mechanism. Blocks the fast sodium channel with slow kinetics, slowing conduction and prolonging the QRS. Its metabolite 5 hydroxypropafenone adds sodium channel block, and the parent adds beta adrenoceptor blockade.

Pharmacodynamics. Oral onset within 1 to 3 hours, peak at 2 to 3 hours. Prolongs PR and QRS in a rate dependent manner; mild bradycardia and negative inotropy.

Pharmacokinetics. Extensive first pass metabolism, with bioavailability that rises with dose. Metabolised by CYP2D6 (to active 5 hydroxypropafenone), CYP3A4 and CYP1A2. Half life 2 to 10 hours in extensive metabolisers and up to 32 hours in poor metabolisers. Excreted in urine and faeces.

Paroxysmal atrial fibrillation or supraventricular tachycardia, prevention, adult.

• Start 150 mg three times daily (12 hourly modified release 225 mg twice daily).

• Increase at 3 to 4 day intervals to 225 mg, then 300 mg three times daily.

• Usual maintenance 150 to 300 mg three times daily; maximum 900 mg daily. Use lower doses under 70 kg and in older adults.

Recent onset atrial fibrillation, single dose ("pill in the pocket"), adult. 450 mg orally for a body weight under 70 kg, or 600 mg for 70 kg and over; give the first dose under observation and use only with a beta blocker or other nodal blocker.

Ventricular arrhythmias (specialist), adult. 150 mg three times daily; maximum 900 mg daily.

Children. Not established; specialist use of 200 mg/m2 daily in 3 divided doses has been described.

Contraindications. Structural heart disease, coronary disease, previous myocardial infarction, heart failure or left ventricular dysfunction; Brugada syndrome; sick sinus syndrome, atrioventricular or bundle branch block without a pacemaker; cardiogenic shock; severe bradycardia, hypotension or electrolyte disturbance; severe obstructive airway disease; myasthenia gravis; hypersensitivity.

Warnings. Proarrhythmia; negative inotropy; bronchospasm in asthma and chronic obstructive disease (beta blocking effect); myasthenic worsening; agranulocytosis (rare); lupus like syndrome; raised pacing thresholds. Large studies after infarction showed higher death rates with class IC drugs.

Adverse effects. Metallic taste, dizziness, nausea, vomiting, constipation, blurred vision, headache, bradycardia, atrioventricular block, proarrhythmia, bronchospasm, rarely liver injury.

Interactions. Digoxin: levels rise by 60 to 80% (reduce the digoxin dose). Warfarin: INR rises. CYP2D6 inhibitors (fluoxetine, paroxetine, quinidine) and CYP3A4 inhibitors (erythromycin, clarithromycin, ketoconazole, ritonavir): levels rise and adverse effects increase. Beta blockers and calcium channel blockers: bradycardia. Ciclosporin: raised levels. Rifampicin: lowers levels. QT prolonging drugs: torsades.

Special groups.

• Pregnancy: avoid unless essential; limited data.

• Breastfeeding: excreted in milk; avoid.

• Patients of African ancestry: no dose change; exclude hypertensive heart disease.

• Older adults: start 150 mg twice daily; accumulation is common.

• Kidney impairment: use lower doses and extend the dose intervals; monitor ECG.

• Liver impairment: reduce the dose by 70 to 80%; avoid in severe disease.

Formulations. Tablets 150 and 300 mg; modified release capsules 225, 325, 425 mg.

Administration. Oral with food in divided doses; swallow modified release capsules whole.

Baseline. ECG (PR, QRS), echocardiogram, potassium, magnesium, liver enzymes, full blood count.

Monitoring. ECG after 3 to 4 days of each dose change and at least yearly; reduce or stop if QRS widens by more than 25% from baseline. Full blood count if fever or infection occurs. Liver enzymes if symptoms. Digoxin level and INR with co prescription.

Stopping. No taper needed.

Common prescribing errors. Prescribing in coronary disease or heart failure; not halving digoxin; omitting a nodal blocker in atrial flutter; using it in asthma; taking it with CYP2D6 inhibitors such as fluoxetine without a dose change.